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Kenneth Daniel Poss

James B. Duke Distinguished Professor Emeritus of Regenerative Biology
Cell Biology
Duke Box 3709, Durham, NC 27710
307 Research Drive, Nanaline Bldg Room 466 A, Durham, NC 27710

Selected Publications


In toto live imaging of Erk signaling dynamics in developing zebrafish hepatocytes.

Journal Article Dev Biol · July 2025 Regional and tissue-wide regulation of signaling pathways orchestrates cellular proliferation and differentiation during organ development. In this study, we established an imaging platform for longitudinal analysis of liver development in live developing ... Full text Link to item Cite

Phased ERK responsiveness and developmental robustness regulate teleost skin morphogenesis.

Journal Article Proc Natl Acad Sci U S A · March 11, 2025 Elongation of the vertebrate embryonic axis necessitates rapid expansion of the epidermis to accommodate the growth of underlying tissues. Here, we generated a toolkit to visualize and quantify signaling in entire cell populations of the periderm, the oute ... Full text Link to item Cite

Hallmarks of regeneration.

Journal Article Cell Stem Cell · September 5, 2024 Regeneration is a heroic biological process that restores tissue architecture and function in the face of day-to-day cell loss or the aftershock of injury. Capacities and mechanisms for regeneration can vary widely among species, organs, and injury context ... Full text Link to item Cite

A screen for regeneration-associated silencer regulatory elements in zebrafish.

Journal Article Dev Cell · March 11, 2024 Regeneration involves gene expression changes explained in part by context-dependent recruitment of transcriptional activators to distal enhancers. Silencers that engage repressive transcriptional complexes are less studied than enhancers and more technica ... Full text Link to item Cite

Preface

Book · January 1, 2024 Cite

In toto imaging of glial JNK signaling during larval zebrafish spinal cord regeneration.

Journal Article Development · December 15, 2023 Identification of signaling events that contribute to innate spinal cord regeneration in zebrafish can uncover new targets for modulating injury responses of the mammalian central nervous system. Using a chemical screen, we identify JNK signaling as a nece ... Full text Link to item Cite

Inter-organ communication during tissue regeneration.

Journal Article Development · December 1, 2023 Tissue regeneration is not simply a local repair event occurring in isolation from the distant, uninjured parts of the body. Rather, evidence indicates that regeneration is a whole-animal process involving coordinated interactions between different organ s ... Full text Link to item Cite

The translation initiation factor homolog eif4e1c regulates cardiomyocyte metabolism and proliferation during heart regeneration.

Journal Article Development · October 15, 2023 The eIF4E family of translation initiation factors bind 5' methylated caps and act as the limiting step for mRNA translation. The canonical eIF4E1A is required for cell viability, yet other related eIF4E families exist and are utilized in specific contexts ... Full text Link to item Cite

Regeneration: Signaling superhighways.

Journal Article Curr Biol · September 25, 2023 Regeneration requires the collective effort of multiple organ systems. A recent study of planarian whole-body regeneration finds that Erk kinase activity propagates rapidly across the entire animal through longitudinal muscle cells to coordinate animal-wid ... Full text Link to item Cite

Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer.

Journal Article Nat Commun · August 11, 2023 Unlike adult mammals, zebrafish regenerate spinal cord tissue and recover locomotor ability after a paralyzing injury. Here, we find that ependymal cells in zebrafish spinal cords produce the neurogenic factor Hb-egfa upon transection injury. Animals with ... Full text Link to item Cite

Progenitor derived glia are required for spinal cord regeneration in zebrafish.

Journal Article Development · May 9, 2023 Unlike mammals, adult zebrafish undergo spontaneous recovery after major spinal cord injury. Whereas reactive gliosis presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish elicit pro-regenerative bridging functions after injury. H ... Full text Link to item Cite

An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

Journal Article Cell Stem Cell · January 5, 2023 The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) i ... Full text Link to item Cite

DeepProjection: specific and robust projection of curved 2D tissue sheets from 3D microscopy using deep learning.

Journal Article Development · November 1, 2022 The efficient extraction of image data from curved tissue sheets embedded in volumetric imaging data remains a serious and unsolved problem in quantitative studies of embryogenesis. Here, we present DeepProjection (DP), a trainable projection algorithm bas ... Full text Link to item Cite

Voltage-gated sodium channel scn8a is required for innervation and regeneration of amputated adult zebrafish fins.

Journal Article Proc Natl Acad Sci U S A · July 12, 2022 Teleost fishes and urodele amphibians can regenerate amputated appendages, whereas this ability is restricted to digit tips in adult mammals. One key component of appendage regeneration is reinnervation of the wound area. However, how innervation is regula ... Full text Link to item Cite

hapln1 Defines an Epicardial Cell Subpopulation Required for Cardiomyocyte Expansion During Heart Morphogenesis and Regeneration.

Journal Article Circulation · July 5, 2022 BACKGROUND: Certain nonmammalian species such as zebrafish have an elevated capacity for innate heart regeneration. Understanding how heart regeneration occurs in these contexts can help illuminate cellular and molecular events that can be targets for hear ... Full text Link to item Cite

Generation of specialized blood vessels via lymphatic transdifferentiation.

Journal Article Nature · June 2022 The lineage and developmental trajectory of a cell are key determinants of cellular identity. In the vascular system, endothelial cells (ECs) of blood and lymphatic vessels differentiate and specialize to cater to the unique physiological demands of each o ... Full text Link to item Cite

Enhancer selection dictates gene expression responses in remote organs during tissue regeneration.

Journal Article Nat Cell Biol · May 2022 Acute trauma stimulates local repair mechanisms but can also impact structures distant from the injury, for example through the activity of circulating factors. To study the responses of remote tissues during tissue regeneration, we profiled transcriptomes ... Full text Link to item Cite

Remote injury responses during zebrafish heart regeneration

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · May 1, 2022 Acute trauma stimulates local repair but can also affect structures distant from the injury, for instance through the activity of circulating factors. To study the responses of remote tissues to injury and regeneration, we generated genome-wide profiles fr ... Full text Cite

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration.

Journal Article Development · February 15, 2022 The epicardium is a mesothelial tissue layer that envelops the heart. Cardiac injury activates dynamic gene expression programs in epicardial tissue, which in zebrafish enables subsequent regeneration through paracrine and vascularizing effects. To identif ... Full text Link to item Cite

The people behind the papers - Yingxi Cao, Ken Poss and Jingli Cao.

Journal Article Development · February 15, 2022 Zebrafish heart regeneration is dependent on the activation of a regenerative programme in the cells surrounding the heart, known as the epicardium. A new paper in Development uses genome-wide transcriptomics and chromatin accessibility profiles to identif ... Full text Link to item Cite

Targeted Delivery for Cardiac Regeneration: Comparison of Intra-coronary Infusion and Intra-myocardial Injection in Porcine Hearts.

Journal Article Front Cardiovasc Med · 2022 BACKGROUND: The optimal delivery route to enhance effectiveness of regenerative therapeutics to the human heart is poorly understood. Direct intra-myocardial (IM) injection is the gold standard, however, it is relatively invasive. We thus compared targeted ... Full text Link to item Cite

Mathematical modeling of Erk activity waves in regenerating zebrafish scales.

Journal Article Biophys J · October 5, 2021 Erk signaling regulates cellular decisions in many biological contexts. Recently, we have reported a series of Erk activity traveling waves that coordinate regeneration of osteoblast tissue in zebrafish scales. These waves originate from a central source r ... Full text Link to item Cite

Regulation of zebrafish fin regeneration by vitamin D signaling.

Journal Article Dev Dyn · September 2021 BACKGROUND: Vitamin D is an essential nutrient that has long been known to regulate skeletal growth and integrity. In models of major appendage regeneration, treatment with vitamin D analogs has been reported to improve aspects of zebrafish fin regeneratio ... Full text Link to item Cite

Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

Journal Article Nat Methods · August 2021 CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both culture ... Full text Link to item Cite

The RNA helicase Ddx52 functions as a growth switch in juvenile zebrafish.

Journal Article Development · July 5, 2021 Vertebrate animals usually display robust growth trajectories during juvenile stages, and reversible suspension of this growth momentum by a single genetic determinant has not been reported. Here, we report a single genetic factor that is essential for juv ... Full text Link to item Cite

Induction of Wnt signaling antagonists and p21-activated kinase enhances cardiomyocyte proliferation during zebrafish heart regeneration.

Journal Article J Mol Cell Biol · April 10, 2021 Heart regeneration occurs by dedifferentiation and proliferation of pre-existing cardiomyocytes (CMs). However, the signaling mechanisms by which injury induces CM renewal remain incompletely understood. Here, we find that cardiac injury in zebrafish induc ... Full text Link to item Cite

In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration.

Journal Article Elife · March 25, 2021 Strategies have not been available until recently to uncover interacting protein networks specific to key cell types, their subcellular compartments, and their major regulators during complex in vivo events. Here, we apply BioID2 proximity labeling to capt ... Full text Link to item Cite

A new society for regenerative biologists.

Journal Article Development · February 12, 2021 Full text Link to item Cite

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.

Journal Article Cell Host Microbe · February 10, 2021 The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains un ... Full text Link to item Cite

Control of osteoblast regeneration by a train of Erk activity waves.

Journal Article Nature · February 2021 Regeneration is a complex chain of events that restores a tissue to its original size and shape. The tissue-wide coordination of cellular dynamics that is needed for proper morphogenesis is challenged by the large dimensions of regenerating body parts. Fee ... Full text Link to item Cite

Ccn2a is an injury-induced matricellular factor that promotes cardiac regeneration in zebrafish.

Journal Article Development · January 18, 2021 The ability of zebrafish to heal their heart after injury makes them an attractive model for investigating the mechanisms governing the regenerative process. In this study, we show that the gene cellular communication network factor 2a (ccn2a), previously ... Full text Link to item Cite

A Genetic Cardiomyocyte Ablation Model for the Study of Heart Regeneration in Zebrafish.

Journal Article Methods Mol Biol · 2021 Adult zebrafish possess an elevated cardiac regenerative capacity as compared with adult mammals. In the past two decades, zebrafish have provided a key model system for studying the cellular and molecular mechanisms of innate heart regeneration. The ease ... Full text Link to item Cite

Preface

Book · January 1, 2021 Cite

Tissue Repair: A Tendon-see to Regenerate.

Journal Article Curr Biol · September 7, 2020 A new study establishes genetic tools to ablate tendon progenitor cells in zebrafish larvae, finding that larval tendons display high regenerative capacity. The authors employ this musculoskeletal repair model to explore the source of tendon progenitors by ... Full text Link to item Cite

Gene regulatory programmes of tissue regeneration.

Journal Article Nat Rev Genet · September 2020 Regeneration is the process by which organisms replace lost or damaged tissue, and regenerative capacity can vary greatly among species, tissues and life stages. Tissue regeneration shares certain hallmarks of embryonic development, in that lineage-specifi ... Full text Link to item Cite

Tp53 Suppression Promotes Cardiomyocyte Proliferation during Zebrafish Heart Regeneration.

Journal Article Cell Rep · September 1, 2020 Zebrafish regenerate heart muscle through division of pre-existing cardiomyocytes. To discover underlying regulation, we assess transcriptome datasets for dynamic gene networks during heart regeneration and identify suppression of genes associated with the ... Full text Link to item Cite

Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration.

Journal Article Development · July 30, 2020 To identify candidate tissue regeneration enhancer elements (TREEs) important for zebrafish fin regeneration, we performed ATAC-seq from bulk tissue or purified fibroblasts of uninjured and regenerating caudal fins. We identified tens of thousands of DNA r ... Full text Link to item Cite

Building bridges, not walls: spinal cord regeneration in zebrafish.

Journal Article Dis Model Mech · May 27, 2020 Spinal cord injury is a devastating condition in which massive cell death and disruption of neural circuitry lead to long-term chronic functional impairment and paralysis. In mammals, spinal cord tissue has minimal capacity to regenerate after injury. In s ... Full text Link to item Cite

Signals for cardiomyocyte proliferation during zebrafish heart regeneration.

Journal Article Curr Opin Physiol · April 2020 The common laboratory zebrafish can regenerate functional cardiac muscle after cataclysmic damage or loss, by activating programs that direct the division of spared cardiomyocytes. Heart regeneration is not a linear series of molecular steps and synchroniz ... Full text Link to item Cite

An array of 60,000 antibodies for proteome-scale antibody generation and target discovery.

Journal Article Sci Adv · March 2020 Antibodies are essential for elucidating gene function. However, affordable technology for proteome-scale antibody generation does not exist. To address this, we developed Proteome Epitope Tag Antibody Library (PETAL) and its array. PETAL consists of 62,20 ... Full text Link to item Cite

Ccn2a/Ctgfa is an injury-induced matricellular factor that promotes cardiac regeneration in zebrafish.

Journal Article Development · January 1, 2020 The ability of zebrafish to heal their heart after injury makes them an attractive model to investigate mechanisms governing the regenerative process. In this study, we show that the gene cellular communication network factor 2a (ccn2a), previously known a ... Full text Link to item Cite

Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart.

Journal Article Elife · December 23, 2019 While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. ... Full text Link to item Cite

Genetic Reprogramming of Positional Memory in a Regenerating Appendage.

Journal Article Curr Biol · December 16, 2019 Certain vertebrates such as salamanders and zebrafish are able to regenerate complex tissues (e.g., limbs and fins) with remarkable fidelity. However, how positional information of the missing structure is recalled by appendage stump cells has puzzled rese ... Full text Link to item Cite

Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.

Journal Article Dev Cell · November 18, 2019 Defective coronary network function and insufficient blood supply are both cause and consequence of myocardial infarction. Efficient revascularization after infarction is essential to support tissue repair and function. Zebrafish hearts exhibit a remarkabl ... Full text Link to item Cite

Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration.

Journal Article Elife · November 8, 2019 In recent years, there has been increasing interest in the role of lymphatics in organ repair and regeneration, due to their importance in immune surveillance and fluid homeostasis. Experimental approaches aimed at boosting lymphangiogenesis following myoc ... Full text Link to item Cite

Can laboratory model systems instruct human limb regeneration?

Journal Article Development · October 2, 2019 Regeneration has fascinated scientists since well before the 20th century revolutions in genetics and molecular biology. The field of regenerative biology has grown steadily over the past decade, incorporating advances in imaging, genomics and genome editi ... Full text Link to item Cite

Vitamin D Stimulates Cardiomyocyte Proliferation and Controls Organ Size and Regeneration in Zebrafish.

Journal Article Dev Cell · March 25, 2019 Attaining proper organ size during development and regeneration hinges on the activity of mitogenic factors. Here, we performed a large-scale chemical screen in embryonic zebrafish to identify cardiomyocyte mitogens. Although commonly considered anti-proli ... Full text Link to item Cite

In Toto Imaging of Dynamic Osteoblast Behaviors in Regenerating Skeletal Bone.

Journal Article Curr Biol · December 17, 2018 Osteoblasts are matrix-depositing cells that can divide and heal bone injuries. Their deep-tissue location and the slow progression of bone regeneration challenge attempts to capture osteoblast behaviors in live tissue at high spatiotemporal resolution. He ... Full text Link to item Cite

A Regeneration Toolkit.

Journal Article Dev Cell · November 5, 2018 The ability of animals to replace injured body parts has been a subject of fascination for centuries. The emerging importance of regenerative medicine has reinvigorated investigations of innate tissue regeneration, and the development of powerful genetic t ... Full text Link to item Cite

Cyclopropane Modification of Trehalose Dimycolate Drives Granuloma Angiogenesis and Mycobacterial Growth through Vegf Signaling.

Journal Article Cell Host Microbe · October 10, 2018 Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively prom ... Full text Link to item Cite

The epicardium as a hub for heart regeneration.

Journal Article Nat Rev Cardiol · October 2018 After decades of directed research, no effective regenerative therapy is currently available to repair the injured human heart. The epicardium, a layer of mesothelial tissue that envelops the heart in all vertebrates, has emerged as a new player in cardiac ... Full text Link to item Cite

Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.

Journal Article Proc Natl Acad Sci U S A · August 28, 2018 During heart development and regeneration, coronary vascularization is tightly coupled with cardiac growth. Although inhibiting vascularization causes defects in the innate regenerative response of zebrafish to heart injury, angiogenic signals are not know ... Full text Link to item Cite

Spine Patterning Is Guided by Segmentation of the Notochord Sheath.

Journal Article Cell Rep · February 20, 2018 The spine is a segmented axial structure made of alternating vertebral bodies (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we show that, prior to centra formation, the outer epithelial cell layer of the zebrafish notochord ... Full text Link to item Cite

Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm.

Journal Article Elife · December 27, 2017 The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required for enhancer activity. Here we examine the transcription-fa ... Full text Link to item Cite

Regeneration Genetics.

Journal Article Annu Rev Genet · November 27, 2017 Understanding how and why animals regenerate complex tissues has the potential to transform regenerative medicine. Here we present an overview of genetic approaches that have recently been applied to dissect mechanisms of regeneration. We describe new adva ... Full text Link to item Cite

Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue.

Journal Article Dev Cell · September 25, 2017 Mechanisms that control cell-cycle dynamics during tissue regeneration require elucidation. Here we find in zebrafish that regeneration of the epicardium, the mesothelial covering of the heart, is mediated by two phenotypically distinct epicardial cell sub ... Full text Link to item Cite

Live fate-mapping of joint-associated fibroblasts visualizes expansion of cell contributions during zebrafish fin regeneration.

Journal Article Development · August 15, 2017 The blastema is a mass of progenitor cells responsible for regeneration of amputated salamander limbs and fish fins. Previous studies have indicated that resident cell sources producing the blastema contribute lineage-restricted progeny to regenerating tis ... Full text Link to item Cite

Cardiac regeneration strategies: Staying young at heart.

Journal Article Science · June 9, 2017 The human heart is continually operating as a muscular pump, contracting, on average, 80 times per minute to propel 8000 liters of blood through body tissues each day. Whereas damaged skeletal muscle has a profound capacity to regenerate, heart muscle, at ... Full text Link to item Cite

Resolving Heart Regeneration by Replacement Histone Profiling.

Journal Article Dev Cell · February 27, 2017 Chromatin regulation is a principal mechanism governing animal development, yet it is unclear to what extent structural changes in chromatin underlie tissue regeneration. Non-mammalian vertebrates such as zebrafish activate cardiomyocyte (CM) division afte ... Full text Link to item Cite

Redirecting cardiac growth mechanisms for therapeutic regeneration.

Journal Article J Clin Invest · February 1, 2017 Heart failure is a major source of morbidity and mortality. Replacing lost myocardium with new tissue is a major goal of regenerative medicine. Unlike adult mammals, zebrafish and neonatal mice are capable of heart regeneration following cardiac injury. In ... Full text Link to item Cite

Deciphering Heart Regeneration by Histone Exchange Profiling.

Conference MOLECULAR BIOLOGY OF THE CELL · January 1, 2017 Link to item Cite

Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca.

Journal Article Development · December 1, 2016 Heightened phenotypic variation among mutant animals is a well-known, but poorly understood phenomenon. One hypothetical mechanism accounting for mutant phenotypic variation is progenitor cells variably choosing between two alternative fates during develop ... Full text Link to item Cite

Live Monitoring of Blastemal Cell Contributions during Appendage Regeneration.

Journal Article Curr Biol · November 21, 2016 The blastema is a mass of progenitor cells that enables regeneration of amputated salamander limbs or fish fins. Methodology to label and track blastemal cell progeny has been deficient, restricting our understanding of appendage regeneration. Here, we cre ... Full text Link to item Cite

Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.

Journal Article Science · November 4, 2016 Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cor ... Full text Link to item Cite

Monitoring Tissue Regeneration at Single-Cell Resolution.

Journal Article Cell Stem Cell · October 6, 2016 For tissue regeneration researchers, seeing is believing. Here, we consider advances in genetic tools, imaging platforms, and quantification capabilities that are turning previously unattainable goals, like in toto capture of cellular and subcellular behav ... Full text Link to item Cite

Accessories to Limb Regeneration.

Journal Article Dev Cell · May 23, 2016 In a recent issue of Nature, Nacu et al. (2016) identified FGF and HH ligands as interacting molecular influences that are necessary and sufficient to induce the formation of supernumerary limbs from blastemal tissue in axolotl salamanders. ... Full text Link to item Cite

Multicolor mapping of the cardiomyocyte proliferation dynamics that construct the atrium.

Journal Article Development · May 15, 2016 The orchestrated division of cardiomyocytes assembles heart chambers of distinct morphology. To understand the structural divergence of the cardiac chambers, we determined the contributions of individual embryonic cardiomyocytes to the atrium in zebrafish ... Full text Link to item Cite

Explant culture of adult zebrafish hearts for epicardial regeneration studies.

Journal Article Nat Protoc · May 2016 Here we describe how to culture adult zebrafish hearts as explants and study the regeneration of epicardial tissue ex vivo, as a means to identify therapeutic targets for heart disease. Uninjured or injured adult hearts are excised, washed and cultured in ... Full text Link to item Cite

Modulation of tissue repair by regeneration enhancer elements.

Journal Article Nature · April 14, 2016 How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lep ... Full text Link to item Cite

Multicolor Cell Barcoding Technology for Long-Term Surveillance of Epithelial Regeneration in Zebrafish.

Journal Article Dev Cell · March 21, 2016 Current fate mapping and imaging platforms are limited in their ability to capture dynamic behaviors of epithelial cells. To deconstruct regenerating adult epithelial tissue at single-cell resolution, we created a multicolor system, skinbow, that barcodes ... Full text Link to item Cite

Building and re-building the heart by cardiomyocyte proliferation.

Journal Article Development · March 1, 2016 The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most- ... Full text Link to item Cite

Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.

Journal Article Development · January 15, 2016 In contrast to mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of cardiomyocytes spared from damage. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration th ... Full text Link to item Cite

Methodologies for Inducing Cardiac Injury and Assaying Regeneration in Adult Zebrafish.

Journal Article Methods Mol Biol · 2016 The zebrafish has emerged as an important model organism for understanding the cellular and molecular mechanisms of tissue regeneration. Adult zebrafish efficiently replace cardiac muscle after partial resection of their ventricle, or after transgenic abla ... Full text Link to item Cite

Myocardial NF-κB activation is essential for zebrafish heart regeneration.

Journal Article Proc Natl Acad Sci U S A · October 27, 2015 Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferati ... Full text Link to item Cite

Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

Journal Article Dev Cell · August 24, 2015 Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studie ... Full text Link to item Cite

Origin, Specification, and Plasticity of the Great Vessels of the Heart.

Journal Article Curr Biol · August 17, 2015 The pharyngeal arch arteries (PAAs) are a series of paired embryonic blood vessels that give rise to several major arteries that connect directly to the heart. During development, the PAAs emerge from nkx2.5-expressing mesodermal cells and connect the dors ... Full text Link to item Cite

Transient laminin beta 1a Induction Defines the Wound Epidermis during Zebrafish Fin Regeneration.

Journal Article PLoS Genet · August 2015 The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed a forward genetic screen for mutations that impair this process in amputa ... Full text Link to item Cite

Myocardium and BMP signaling are required for endocardial differentiation.

Journal Article Development · July 1, 2015 Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm and migrate to the midline where they coalesce to form the cardiac tube. Endocardial progenitors acquire a molecular identity distinct from other va ... Full text Link to item Cite

Back in Black.

Journal Article Dev Cell · June 22, 2015 In this issue of Developmental Cell, Iyengar and colleagues (2015) employ live imaging of melanocyte regeneration in adult zebrafish to define a bias in progenitor cell fates that enables both rapid pigment cell renewal and maintenance of regenerative capa ... Full text Link to item Cite

Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling.

Journal Article Nature · June 11, 2015 In response to cardiac damage, a mesothelial tissue layer enveloping the heart called the epicardium is activated to proliferate and accumulate at the injury site. Recent studies have implicated the epicardium in multiple aspects of cardiac repair: as a so ... Full text Link to item Cite

Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish.

Journal Article Elife · April 1, 2015 Heart regeneration is limited in adult mammals but occurs naturally in adult zebrafish through the activation of cardiomyocyte division. Several components of the cardiac injury microenvironment have been identified, yet no factor on its own is known to st ... Full text Open Access Link to item Cite

Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration.

Journal Article Development · August 2014 Embryonic heart formation requires the production of an appropriate number of cardiomyocytes; likewise, cardiac regeneration following injury relies upon the recovery of lost cardiomyocytes. The basic helix-loop-helix (bHLH) transcription factor Hand2 has ... Full text Link to item Cite

Keeping at arm's length during regeneration.

Journal Article Dev Cell · April 28, 2014 Regeneration of a lost appendage in adult amphibians and fish is a remarkable feat of developmental patterning. Although the limb or fin may be years removed from its initial creation by an embryonic primordium, the blastema that emerges at the injury site ... Full text Link to item Cite

zebraflash transgenic lines for in vivo bioluminescence imaging of stem cells and regeneration in adult zebrafish.

Journal Article Development · December 2013 The zebrafish has become a standard model system for stem cell and tissue regeneration research, based on powerful genetics, high tissue regenerative capacity and low maintenance costs. Yet, these studies can be challenged by current limitations of tissue ... Full text Link to item Cite

The zebrafish as a model for complex tissue regeneration.

Journal Article Trends Genet · November 2013 For centuries, philosophers and scientists have been fascinated by the principles and implications of regeneration in lower vertebrate species. Two features have made zebrafish an informative model system for determining mechanisms of regenerative events. ... Full text Link to item Cite

Fibronectin is deposited by injury-activated epicardial cells and is necessary for zebrafish heart regeneration.

Journal Article Dev Biol · October 15, 2013 Unlike adult mammals, adult zebrafish vigorously regenerate lost heart muscle in response to injury. The epicardium, a mesothelial cell layer enveloping the myocardium, is activated to proliferate after cardiac injury and can contribute vascular support ce ... Full text Link to item Cite

Local Dkk1 crosstalk from breeding ornaments impedes regeneration of injured male zebrafish fins.

Journal Article Dev Cell · October 14, 2013 Precise spatiotemporal regulation of signaling activators and inhibitors can help limit developmental crosstalk between neighboring tissues during morphogenesis, homeostasis, and regeneration. Here, we find that the secreted Wnt inhibitor Dkk1b is abundant ... Full text Link to item Cite

Transcriptional components of anteroposterior positional information during zebrafish fin regeneration.

Journal Article Development · September 2013 Many fish and salamander species regenerate amputated fins or limbs, restoring the size and shape of the original appendage. Regeneration requires that spared cells retain or recall information encoding pattern, a phenomenon termed positional memory. Few f ... Full text Link to item Cite

Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi.

Journal Article Development · September 2013 Striated muscle development requires the coordinated expression of genes involved in sarcomere formation and contractility, as well as genes that determine muscle morphology. However, relatively little is known about the molecular mechanisms that control t ... Full text Link to item Cite

Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration.

Journal Article Proc Natl Acad Sci U S A · August 13, 2013 Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes ... Full text Link to item Cite

An injury-responsive gata4 program shapes the zebrafish cardiac ventricle.

Journal Article Curr Biol · July 8, 2013 A common principle of tissue regeneration is the reactivation of previously employed developmental programs. During zebrafish heart regeneration, cardiomyocytes in the cortical layer of the ventricle induce the transcription factor gene gata4 and prolifera ... Full text Link to item Cite

A novel chemical screening strategy in zebrafish identifies common pathways in embryogenesis and rhabdomyosarcoma development.

Journal Article Development · June 2013 The zebrafish is a powerful genetic model that has only recently been used to dissect developmental pathways involved in oncogenesis. We hypothesized that operative pathways during embryogenesis would also be used for oncogenesis. In an effort to define RA ... Full text Link to item Cite

Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function.

Journal Article Development · March 2013 Second heart field (SHF) progenitors perform essential functions during mammalian cardiogenesis. We recently identified a population of cardiac progenitor cells (CPCs) in zebrafish expressing latent TGFβ-binding protein 3 (ltbp3) that exhibits several defi ... Full text Link to item Cite

In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration.

Journal Article Development · February 1, 2013 Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury, a deficiency that underlies the poor regenerative ability of human hearts after myocardial infarction. By contrast, zebrafish regenerate heart muscle after trauma by ... Full text Link to item Cite

Toward a blueprint for regeneration.

Journal Article Development · August 2012 Tissue regeneration has been studied for hundreds of years, yet remains one of the less understood topics in developmental biology. The recent Keystone Symposium on Mechanisms of Whole Organ Regeneration brought together biologists, clinicians and bioengin ... Full text Link to item Cite

Regulation of zebrafish heart regeneration by miR-133.

Journal Article Dev Biol · May 15, 2012 Zebrafish regenerate cardiac muscle after severe injuries through the activation and proliferation of spared cardiomyocytes. Little is known about factors that control these events. Here we investigated the extent to which miRNAs regulate zebrafish heart r ... Full text Link to item Cite

Clonally dominant cardiomyocytes direct heart morphogenesis.

Journal Article Nature · April 25, 2012 As vertebrate embryos develop to adulthood, their organs undergo marked changes in size and tissue architecture. The heart acquires muscle mass and matures structurally to fulfil increasing circulatory needs, a process that is incompletely understood. Here ... Full text Link to item Cite

Regeneration of amputated zebrafish fin rays from de novo osteoblasts.

Journal Article Dev Cell · April 17, 2012 Determining the cellular source of new skeletal elements is critical for understanding appendage regeneration in amphibians and fish. Recent lineage-tracing studies indicated that zebrafish fin ray bone regenerates through the dedifferentiation and prolife ... Full text Link to item Cite

Cardiac regeneration.

Journal Article Curr Top Dev Biol · 2012 The heart is a pump that is comprised of cardiac myocytes and other cell types and whose proper function is critical to quality of life. The ability to trigger regeneration of heart muscle following injury eludes adult mammals, a deficiency of great clinic ... Full text Link to item Cite

Cardiac regenerative capacity and mechanisms.

Journal Article Annu Rev Cell Dev Biol · 2012 The heart holds the monumental yet monotonous task of maintaining circulation. Although cardiac function is critical to other organs and to life itself, mammals are not equipped with significant natural capacity to replace heart muscle that has been lost b ... Full text Link to item Cite

Sexually dimorphic fin regeneration in zebrafish controlled by androgen/GSK3 signaling.

Journal Article Curr Biol · November 22, 2011 Certain fish and amphibians regenerate entire fins and limbs after amputation, whereas such potential is absent in birds and limited in mammals to digit tips [1, 2]. Additionally, regenerative success can change during life stages. Anuran tadpoles graduall ... Full text Link to item Cite

FGF signaling regulates rod photoreceptor cell maintenance and regeneration in zebrafish.

Journal Article Exp Eye Res · November 2011 Fgf signaling is required for many biological processes involving the regulation of cell proliferation and maintenance, including embryonic patterning, tissue homeostasis, wound healing, and cancer progression. Although the function of Fgf signaling is sug ... Full text Link to item Cite

The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion.

Journal Article Development · August 2011 Natural models of heart regeneration in lower vertebrates such as zebrafish are based on invasive surgeries causing mechanical injuries that are limited in size. Here, we created a genetic cell ablation model in zebrafish that facilitates inducible destruc ... Full text Link to item Cite

tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration.

Journal Article Development · July 2011 Recent lineage-tracing studies have produced conflicting results about whether the epicardium is a source of cardiac muscle cells during heart development. Here, we examined the developmental potential of epicardial tissue in zebrafish during both embryoni ... Full text Link to item Cite

Restriction of hepatic competence by Fgf signaling.

Journal Article Development · April 2011 Hepatic competence, or the ability to respond to hepatic-inducing signals, is regulated by a number of transcription factors broadly expressed in the endoderm. However, extrinsic signals might also regulate hepatic competence, as suggested by tissue explan ... Full text Link to item Cite

Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration.

Journal Article Dev Cell · March 15, 2011 Featured Publication Zebrafish heart regeneration occurs through the activation of cardiomyocyte proliferation in areas of trauma. Here, we show that within 3 hr of ventricular injury, the entire endocardium undergoes morphological changes and induces expression of the retinoi ... Full text Link to item Cite

Cardiac Regeneration in the Zebrafish Model System

Journal Article · December 1, 2010 This chapter reviews what is known about mechanisms of heart regeneration in zebrafish. In addition to addressing "how" regeneration occurs, it will touch on questions of "why." That is, why is the capacity for natural heart regeneration limited to nonmamm ... Full text Cite

A dual role for ErbB2 signaling in cardiac trabeculation.

Journal Article Development · November 2010 Cardiac trabeculation is a crucial morphogenetic process by which clusters of ventricular cardiomyocytes extrude and expand into the cardiac jelly to form sheet-like projections. Although it has been suggested that cardiac trabeculae enhance cardiac contra ... Full text Open Access Link to item Cite

Advances in understanding tissue regenerative capacity and mechanisms in animals.

Journal Article Nat Rev Genet · October 2010 Featured Publication Questions about how and why tissue regeneration occurs have captured the attention of countless biologists, biomedical engineers and clinicians. Regenerative capacity differs greatly across organs and organisms, and a range of model systems that use differ ... Full text Link to item Cite

Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish.

Journal Article Dev Cell · June 15, 2010 Extracellular matrix (ECM) remodeling is critical for organogenesis, yet its molecular regulation is poorly understood. In zebrafish, asymmetric migration of the epithelial lateral plate mesoderm (LPM) displaces the gut leftward, allowing correct placement ... Full text Link to item Cite

Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes.

Journal Article Nature · March 25, 2010 Featured Publication Recent studies indicate that mammals, including humans, maintain some capacity to renew cardiomyocytes throughout postnatal life. Yet, there is little or no significant cardiac muscle regeneration after an injury such as acute myocardial infarction. By con ... Full text Link to item Cite

Neuronal regulation of the spatial patterning of neurogenesis.

Journal Article Dev Cell · January 19, 2010 Precise regulation of neurogenesis is achieved in specific regions of the vertebrate nervous system by formation of distinct neurogenic and nonneurogenic zones. We have investigated how neurogenesis becomes confined to zones adjacent to rhombomere boundari ... Full text Link to item Cite

Cardiac Regeneration in the Zebrafish Model System

Chapter · January 1, 2010 This chapter reviews what is known about mechanisms of heart regeneration in zebrafish. In addition to addressing “how” regeneration occurs, it will touch on questions of “why.” That is, why is the capacity for natural heart regeneration limited to nonmamm ... Full text Cite

Ras controls melanocyte expansion during zebrafish fin stripe regeneration.

Journal Article Dis Model Mech · 2010 Regenerative medicine for complex tissues like limbs will require the provision or activation of precursors for different cell types, in the correct number, and with the appropriate instructions. These strategies can be guided by what is learned from spect ... Full text Open Access Link to item Cite

Maintenance of blastemal proliferation by functionally diverse epidermis in regenerating zebrafish fins.

Journal Article Dev Biol · July 15, 2009 Appendage regeneration in salamanders and fish occurs through formation and maintenance of a mass of progenitor tissue called the blastema. A dedicated epidermis overlays the blastema and is required for its proliferation and patterning, yet this interacti ... Full text Link to item Cite

Feedback regulation of neurogenesis

Journal Article Developmental Biology · July 2009 Full text Cite

Genetic DISC-section of regeneration in Drosophila.

Journal Article Dev Cell · June 2009 Although regeneration has long fascinated biologists, it remains a challenging field of study with much yet to learn at the molecular level. In this issue of Developmental Cell, Smith-Bolton et al. introduce a genetic ablation system in Drosophila melanoga ... Full text Link to item Cite

Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish.

Journal Article Dev Cell · December 2008 How adjacent organ fields communicate during development is not understood. Here, we identify a mechanism in which signaling within the forelimb field restricts the potential of the neighboring heart field. In zebrafish embryos deficient in retinoic acid ( ... Full text Link to item Cite

Reiterative roles for FGF signaling in the establishment of size and proportion of the zebrafish heart.

Journal Article Dev Biol · September 15, 2008 Development of a functional organ requires the establishment of its proper size as well as the establishment of the relative proportions of its individual components. In the zebrafish heart, organ size and proportion depend heavily on the number of cells i ... Full text Link to item Cite

Fgfs control homeostatic regeneration in adult zebrafish fins.

Journal Article Development · September 2008 Adult teleost fish and urodele amphibians possess a spectacular ability to regenerate amputated appendages, based on formation and maintenance of progenitor tissue called a blastema. Although injury-induced, or facultative, appendage regeneration has been ... Full text Link to item Cite

New regulators of vertebrate appendage regeneration.

Journal Article Curr Opin Genet Dev · August 2008 Appendage regeneration is a complex and fascinating biological process exhibited in vertebrates by urodele amphibians and teleost fish. A current focus in the field is to identify new molecules that control formation and function of the regeneration blaste ... Full text Link to item Cite

Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish.

Journal Article Genes Dev · March 15, 2008 Featured Publication Appendage regeneration is defined by rapid changes in gene expression that achieve dramatic developmental effects, suggesting involvement of microRNAs (miRNAs). Here, we find dynamic regulation of many miRNAs during zebrafish fin regeneration. In particula ... Full text Link to item Cite

Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish.

Journal Article Development · January 2008 Featured Publication The heart maintains structural and functional integrity during years of continual contraction, but the extent to which new cell creation participates in cardiac homeostasis is unclear. Here, we assessed cellular and molecular mechanisms of cardiac homeosta ... Full text Link to item Cite

Cardiac progenitors during zebrafish heart regeneration

Conference CIRCULATION RESEARCH · August 31, 2007 Link to item Cite

Bmp and Fgf signaling are essential for liver specification in zebrafish.

Journal Article Development · June 2007 Based on data from in vitro tissue explant and ex vivo cell/bead implantation experiments, Bmp and Fgf signaling have been proposed to regulate hepatic specification. However, genetic evidence for this hypothesis has been lacking. Here, we provide in vivo ... Full text Link to item Cite

Specification of epibranchial placodes in zebrafish.

Journal Article Development · February 2007 In all vertebrates, the neurogenic placodes are transient ectodermal thickenings that give rise to sensory neurons of the cranial ganglia. Epibranchial (EB) placodes generate neurons of the distal facial, glossopharyngeal and vagal ganglia, which convey se ... Full text Link to item Cite

Getting to the heart of regeneration in zebrafish.

Journal Article Semin Cell Dev Biol · February 2007 A scientific and clinical prerogative of the 21st century is to stimulate the regenerative ability of the human heart. While the mammalian heart shows little or no natural regeneration in response to injury, certain non-mammalian vertebrates possess an ele ... Full text Link to item Cite

Zebrafish Heart Regeneration as a Model for Cardiac Tissue Repair.

Journal Article Drug Discov Today Dis Models · 2007 Heart disease remains the leading cause of mortality throughout the world. Mammals have an extremely limited capacity to repair lost or damaged heart tissue, thus encouraging biologists to seek out models for heart regeneration. Zebrafish exhibit a robust ... Full text Link to item Cite

A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration.

Journal Article Cell · November 3, 2006 Zebrafish possess a unique yet poorly understood capacity for cardiac regeneration. Here, we show that regeneration proceeds through two coordinated stages following resection of the ventricular apex. First a blastema is formed, comprised of progenitor cel ... Full text Link to item Cite

Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration.

Journal Article Development · December 2005 During appendage regeneration in urodeles and teleosts, tissue replacement is precisely regulated such that only the appropriate structures are recovered, a phenomenon referred to as positional memory. It is believed that there exists, or is quickly establ ... Full text Link to item Cite

A zebrafish model of germ cell aneuploidy.

Journal Article Cell Cycle · October 2004 The high frequency of chromosomal nondisjunction in human germ cells impacts society in many ways. Yet, the etiology of chromosome disorders remains unclear. Using a zebrafish strain with a hypomorphic mutation in the kinase Mps1, a genetic association bet ... Full text Link to item Cite

Germ cell aneuploidy in zebrafish with mutations in the mitotic checkpoint gene mps1.

Journal Article Genes Dev · July 1, 2004 Aneuploidy, resulting from chromosome missegregation during meiosis, is a major cause of human infertility and birth defects. However, its molecular basis remains incompletely understood. Here we have identified a spectrum of chromosome anomalies in embryo ... Full text Link to item Cite

Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants.

Journal Article Nat Immunol · December 2003 The zebrafish is firmly established as a genetic model for the study of vertebrate blood development. Here we have characterized the blood-forming system of adult zebrafish. Each major blood lineage can be isolated by flow cytometry, and with these lineal ... Full text Link to item Cite

Positional cloning of a temperature-sensitive mutant emmental reveals a role for sly1 during cell proliferation in zebrafish fin regeneration.

Journal Article Dev Biol · June 15, 2003 Here, we used classical genetics in zebrafish to identify temperature-sensitive mutants in caudal fin regeneration. Gross morphological, histological, and molecular analyses revealed that one of these strains, emmental (emm), failed to form a functional re ... Full text Link to item Cite

Tales of regeneration in zebrafish.

Journal Article Dev Dyn · February 2003 Complex tissue regeneration involves exquisitely coordinated proliferation and patterning of adult cells after severe injury or amputation. Certain lower vertebrates such as urodele amphibians and teleost fish have a greater capacity for regeneration than ... Full text Link to item Cite

Changes in gravitational force induce alterations in gene expression that can be monitored in the live, developing zebrafish heart.

Journal Article Adv Space Res · 2003 Little is known about the effect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a beta-actin promoter, we examined the affect of simulated-m ... Full text Link to item Cite

Heart regeneration in zebrafish.

Journal Article Science · December 13, 2002 Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Regeneration occurs th ... Full text Link to item Cite

Mps1 defines a proximal blastemal proliferative compartment essential for zebrafish fin regeneration.

Journal Article Development · November 2002 One possible reason why regeneration remains enigmatic is that the dominant organisms used for studying regeneration are not amenable to genetic approaches. We mutagenized zebrafish and screened for temperature-sensitive defects in adult fin regeneration. ... Full text Link to item Cite

Induction of lef1 during zebrafish fin regeneration.

Journal Article Dev Dyn · October 2000 Because the transcription factor Lef1 is important for development of several vertebrate organs but has not been investigated for involvement in epimorphic regeneration, we examined its expression during regeneration of amputated adult zebrafish caudal fin ... Full text Link to item Cite

Roles for Fgf signaling during zebrafish fin regeneration.

Journal Article Dev Biol · June 15, 2000 Following amputation of a urodele limb or teleost fin, the formation of a blastema is a crucial step in facilitating subsequent regeneration. Using the zebrafish caudal fin regeneration model, we have examined the hypothesis that fibroblast growth factors ... Full text Link to item Cite

The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo.

Journal Article Am J Pathol · May 2000 Heme oxygenase (HO) is the rate limiting enzyme in the degradation of heme, and its isozyme, HO-1, may protect against tissue injury. One posited mechanism is the degradation of heme released from destabilized heme proteins. We demonstrate that HO-1 is a c ... Full text Link to item Cite

Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis.

Journal Article Am J Physiol Renal Physiol · May 2000 Heme oxygenase-1 (HO-1) is a 32-kDa microsomal enzyme that catalyzes the conversion of heme to biliverdin, releasing iron and carbon monoxide. Induction of HO-1 occurs as a protective response in cells/tissues exposed to a wide variety of oxidant stimuli. ... Full text Link to item Cite

Circadian locomotor rhythms in mice with targeted disruption of the gene for the carbon monoxide synthesizing enzyme, heme oxygenase-2

Journal Article Biological Rhythm Research · October 27, 1999 Carbon monoxide (CO), generated in neurons by the enzyme heme oxygenase- 2 (HO2), is postulated to be a gaseous signaling molecule in the mammalian brain. Because of the recent evidence suggesting an important role of another endogenously produced gas, nit ... Full text Cite

Haem oxygenase-1 prevents cell death by regulating cellular iron.

Journal Article Nat Cell Biol · July 1999 Haem oxygenase-1 (HO1) is a heat-shock protein that is induced by stressful stimuli. Here we demonstrate a cytoprotective role for HO1: cell death produced by serum deprivation, staurosporine or etoposide is markedly accentuated in cells from mice with a t ... Full text Link to item Cite

Expression of heme oxygenase-1 can determine cardiac xenograft survival.

Journal Article Nat Med · September 1998 The rejection of concordant xenografts, such as mouse-to-rat cardiac xenografts, is very similar to the delayed rejection of porcine-to-primate discordant xenografts. In concordant models, this type of rejection is prevented by brief complement inhibition ... Full text Link to item Cite

Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2.

Journal Article J Clin Invest · March 1, 1998 Heme oxygenase (HO) activity leads to accumulation of the antioxidant bilirubin, and degradation of the prooxidant heme. Moderate overexpression of the inducible form, HO-1, is associated with protection against oxidative injury. However, the role of HO-2 ... Full text Link to item Cite

Ejaculatory abnormalities in mice with targeted disruption of the gene for heme oxygenase-2.

Journal Article Nat Med · January 1998 Nitric oxide (NO) is well established as a neurotransmitter in the central and peripheral nervous systems. More recently, another gas, carbon monoxide (CO) has also been implicated in neurotransmission. In the nervous system CO is formed by a subtype of he ... Full text Link to item Cite

Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide.

Journal Article Proc Natl Acad Sci U S A · December 23, 1997 Neuronal nitric oxide synthase (nNOS) generates NO in neurons, and heme-oxygenase-2 (HO-2) synthesizes carbon monoxide (CO). We have evaluated the roles of NO and CO in intestinal neurotransmission using mice with targeted deletions of nNOS or HO-2. Immuno ... Full text Link to item Cite

Heme oxygenase 1 is required for mammalian iron reutilization.

Journal Article Proc Natl Acad Sci U S A · September 30, 1997 The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to b ... Full text Link to item Cite

Reduced stress defense in heme oxygenase 1-deficient cells.

Journal Article Proc Natl Acad Sci U S A · September 30, 1997 Stressed mammalian cells up-regulate heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells fro ... Full text Link to item Cite

Hippocampal long-term potentiation is normal in heme oxygenase-2 mutant mice.

Journal Article Neuron · October 1995 We have generated mice deficient in HO-2, the major cerebral isoform of heme oxygenase, in order to assess the potential role of carbon monoxide as a retrograde messenger in hippocampal LTP. Cerebral HO catalytic activity was markedly reduced in the HO-2 m ... Full text Link to item Cite