Scholars@Duke
Stefano Di Talia

Stefano Di Talia

Professor of Cell Biology
Cell Biology

Selected Publications

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

Developmental Control of Cell Cycle and Signaling.

Journal Article Cold Spring Harb Perspect Biol · February 3, 2025 In most species, the earliest stages of embryogenesis are characterized by rapid proliferation, which must be tightly controlled with other cellular processes across the large scale of the embryo. The study of this coordination has recently revealed new me ... Full text Link to item Cite

The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos.

Journal Article Curr Biol · February 3, 2025 Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes.1,2,3 The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm.4,5,6,7 Yet, the rela ... Full text Link to item Cite

Topological interactions drive the first fate decision in the Drosophila embryo

Journal Article Nature Physics · January 1, 2025 During embryogenesis, the first cell fate decision—whether the cell participates in development of the embryo or not—is often linked to the positioning of the nucleus. The cell cycle oscillator and associated cytoskeletal dynamics contribute to the control ... Full text Cite

The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos.

Journal Article bioRxiv · December 15, 2024 Anaphase is tightly controlled in space and time to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm. Yet, the relationship be ... Full text Link to item Cite

Notochord segmentation in zebrafish controlled by iterative mechanical signaling.

Journal Article Dev Cell · July 22, 2024 In bony fishes, patterning of the vertebral column, or spine, is guided by a metameric blueprint established in the notochord sheath. Notochord segmentation begins days after somitogenesis concludes and can occur in its absence. However, somite patterning ... Full text Link to item Cite

The maternal-to-zygotic transition.

Journal Article Curr Biol · June 3, 2024 Rapid cleavage divisions and the transition from maternal to zygotic control of gene expression are the hallmarks of early embryonic development in most species. Early development in insects, fish and amphibians is characterized by several short cell cycle ... Full text Link to item Cite

Robust cytoplasmic partitioning by solving an intrinsic cytoskeletal instability.

Journal Article bioRxiv · March 13, 2024 Early development across vertebrates and insects critically relies on robustly reorganizing the cytoplasm of fertilized eggs into individualized cells. This intricate process is orchestrated by large microtubule structures that traverse the embryo, partiti ... Full text Link to item Cite

Pluripotency of a founding field: rebranding developmental biology.

Journal Article Development · February 1, 2024 The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field ... Full text Link to item 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

Two-fluid dynamics and micron-thin boundary layers shape cytoplasmic flows in early Drosophila embryos.

Journal Article Proc Natl Acad Sci U S A · October 31, 2023 Cytoplasmic flows are widely emerging as key functional players in development. In early Drosophila embryos, flows drive the spreading of nuclei across the embryo. Here, we combine hydrodynamic modeling with quantitative imaging to develop a two-fluid mode ... Full text Link to item Cite

An active traveling wave of Eda/NF-κB signaling controls the timing and hexagonal pattern of skin appendages in zebrafish.

Journal Article Development · September 15, 2023 Periodic patterns drive the formation of a variety of tissues, including skin appendages such as feathers and scales. Skin appendages serve important and diverse functions across vertebrates, yet the mechanisms that regulate their patterning are not fully ... Full text Link to item Cite

Dynamic BMP signaling mediates notochord segmentation in zebrafish.

Journal Article Curr Biol · June 19, 2023 The vertebrate spine is a metameric structure composed of alternating vertebral bodies (centra) and intervertebral discs.1 Recent studies in zebrafish have shown that the epithelial sheath surrounding the notochord differentiates into alternating cartilage ... Full text Link to item Cite

Axial segmentation by iterative mechanical signaling.

Journal Article bioRxiv · March 28, 2023 In bony fishes, formation of the vertebral column, or spine, is guided by a metameric blueprint established in the epithelial sheath of the notochord. Generation of the notochord template begins days after somitogenesis and even occurs in the absence of so ... Full text Link to item Cite

Reconstruction and deconstruction of human somitogenesis in vitro.

Journal Article Nature · February 2023 The vertebrate body displays a segmental organization that is most conspicuous in the periodic organization of the vertebral column and peripheral nerves. This metameric organization is first implemented when somites, which contain the precursors of skelet ... Full text Link to item Cite

An active traveling wave of Eda/NF-kB signaling controls the timing and hexagonal pattern of skin appendages in zebrafish

Journal Article · 2023 Periodic patterns make up a variety of tissues, including skin appendages such as feathers and scales. Skin appendages serve important and diverse functions across vertebrates, yet the mechanisms that regulate their patterning are not fully understood. Her ... Full text Cite

A wave of NF-κB activity regulates zebrafish scale development

Conference MOLECULAR BIOLOGY OF THE CELL · 2023 Cite

Structure-function analysis of Cdc25Twine degradation at the Drosophila maternal-to-zygotic transition.

Journal Article Fly (Austin) · December 2022 Downregulation of protein phosphatase Cdc25Twine activity is linked to remodelling of the cell cycle during the Drosophila maternal-to-zygotic transition (MZT). Here, we present a structure-function analysis of Cdc25Twine. We use chimeras to show that the ... Full text Link to item Cite

Manipulating the nature of embryonic mitotic waves.

Journal Article Curr Biol · November 21, 2022 Early embryogenesis is characterized by rapid and synchronous cleavage divisions, which are often controlled by wave-like patterns of Cdk1 activity. Two mechanisms have been proposed for mitotic waves: sweep and trigger waves.1,2 The two mechanisms give ri ... 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

Morphogenetic Roles of Hydrostatic Pressure in Animal Development.

Journal Article Annu Rev Cell Dev Biol · October 6, 2022 During organismal development, organs and systems are built following a genetic blueprint that produces structures capable of performing specific physiological functions. Interestingly, we have learned that the physiological activities of developing tissue ... Full text Link to item Cite

Geometry and symmetry-breaking in cell polarity.

Journal Article Nat Comput Sci · August 2022 Full text Link to item Cite

Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.

Journal Article Curr Biol · May 9, 2022 In most metazoans, early embryonic development is characterized by rapid division cycles that pause before gastrulation at the midblastula transition (MBT).1 These cleavage divisions are accompanied by cytoskeletal rearrangements that ensure proper nuclear ... Full text Link to item Cite

Waves in Embryonic Development.

Journal Article Annu Rev Biophys · May 9, 2022 Embryonic development hinges on effective coordination of molecular events across space and time. Waves have recently emerged as constituting an ubiquitous mechanism that ensures rapid spreading of regulatory signals across embryos, as well as reliable con ... Full text Link to item Cite

DeepProjection: Rapid and structure-specific projections of tissue sheets embedded in 3D microscopy stacks using deep learning

Journal Article bioRxiv · November 17, 2021 AbstractThe efficient extraction of local high-resolution content from massive amounts of imaging data remains a serious and unsolved problem in studies of complex biological tissues. Here we present DeepProjection, a train ... Full text 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

Cell cycle control during early embryogenesis.

Journal Article Development · July 1, 2021 Understanding the mechanisms of embryonic cell cycles is a central goal of developmental biology, as the regulation of the cell cycle must be closely coordinated with other events during early embryogenesis. Quantitative imaging approaches have recently be ... Full text Link to item Cite

Roadmap for the multiscale coupling of biochemical and mechanical signals during development.

Journal Article Phys Biol · April 14, 2021 The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientis ... Full text Link to item Cite

Temperature-Induced uncoupling of cell cycle regulators.

Conference Dev Biol · February 2021 The early stages of development involve complex sequences of morphological changes that are both reproducible from embryo to embryo and often robust to environmental variability. To investigate the relationship between reproducibility and robustness we exa ... 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

CDK-Regulated Phase Separation Seeded by Histone Genes Ensures Precise Growth and Function of Histone Locus Bodies.

Journal Article Dev Cell · August 10, 2020 Many membraneless organelles form through liquid-liquid phase separation, but how their size is controlled and whether size is linked to function remain poorly understood. The histone locus body (HLB) is an evolutionarily conserved nuclear body that regula ... Full text Link to item Cite

Self-Organized Nuclear Positioning Synchronizes the Cell Cycle in Drosophila Embryos.

Journal Article Cell · May 2, 2019 The synchronous cleavage divisions of early embryogenesis require coordination of the cell-cycle oscillator, the dynamics of the cytoskeleton, and the cytoplasm. Yet, it remains unclear how spatially restricted biochemical signals are integrated with physi ... Full text Link to item Cite

Developmental Biology: Embryos Need to Control Their Nucleotides Just Right.

Journal Article Curr Biol · April 1, 2019 The maternal-to-zygotic transition in the Drosophila embryo requires accurate control of the levels of free nucleotides, arguing for an essential role of nucleotide metabolism in the regulation of the cell cycle during early embryogenesis. ... 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

Chemical Waves in Embryonic Cell Cycles

Journal Article Israel Journal of Chemistry · June 1, 2018 In most metazoans, early embryonic development is characterized by a rapid series of cleavage divisions. At the core of the coordination of these divisions is the oscillatory dynamic of Cyclin-dependent kinase 1 (Cdk1), which arises through the integration ... Full text Cite

Chemical waves in cell and developmental biology.

Journal Article J Cell Biol · April 2, 2018 Many biological events, such as the propagation of nerve impulses, the synchronized cell cycles of early embryogenesis, and collective cell migration, must be coordinated with remarkable speed across very large distances. Such rapid coordination cannot be ... Full text Link to item Cite

Mitotic waves in the early embryogenesis of Drosophila: Bistability traded for speed.

Journal Article Proc Natl Acad Sci U S A · March 6, 2018 Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. Chemical waves of Cdk1 activity were previously shown to spread across Drosophila embryos, and the underlying molecular processes were dissected. Here, we p ... 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

For Embryos, Mother Can Only Take You So Far.

Journal Article Dev Cell · August 7, 2017 Early embryonic development is characterized by rapid cleavage divisions, which impose significant constraints on metabolic pathways. In this issue, Song et al. (2017) show that Drosophila embryos synthesize a large fraction of nucleotides on the go and th ... 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

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

Transcriptional Timers Regulating Mitosis in Early Drosophila Embryos.

Journal Article Cell Rep · September 13, 2016 The development of an embryo requires precise spatiotemporal regulation of cellular processes. During Drosophila gastrulation, a precise temporal pattern of cell division is encoded through transcriptional regulation of cdc25(string) in 25 distinct mitotic ... Full text Link to item Cite

Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos.

Journal Article Dev Cell · August 22, 2016 Embryos of most metazoans undergo rapid and synchronous cell cycles following fertilization. While diffusion is too slow for synchronization of mitosis across large spatial scales, waves of Cdk1 activity represent a possible process of synchronization. How ... Full text Link to item Cite

Measuring time during early embryonic development.

Journal Article Semin Cell Dev Biol · July 2016 In most metazoans, embryonic development is orchestrated by a precise series of cellular behaviors. Understanding how such events are regulated to achieve a stereotypical temporal progression is a fundamental problem in developmental biology. In this revie ... 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

Heterogeneities in Nanog Expression Drive Stable Commitment to Pluripotency in the Mouse Blastocyst.

Journal Article Cell Rep · March 10, 2015 The pluripotent epiblast (EPI) is the founder tissue of almost all somatic cells. EPI and primitive endoderm (PrE) progenitors arise from the inner cell mass (ICM) of the blastocyst-stage embryo. The EPI lineage is distinctly identified by its expression o ... Full text Link to item Cite

Quantitative analyses for elucidating mechanisms of cell fate commitment in the mouse blastocyst

Conference Progress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2015 In recent years we have witnessed a shift from qualitative image analysis towards higher resolution, quantitative analyses of imaging data in developmental biology. This shift has been fueled by technological advances in both imaging and analysis software. ... Full text Cite

Simple biochemical pathways far from steady state can provide switchlike and integrated responses.

Journal Article Biophys J · August 5, 2014 Covalent modification cycles (systems in which the activity of a substrate is regulated by the action of two opposing enzymes) and ligand/receptor interactions are ubiquitous in signaling systems and their steady-state properties are well understood. Howev ... Full text Link to item Cite

GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst.

Journal Article Dev Cell · May 27, 2014 Cells of the inner cell mass (ICM) of the mouse blastocyst differentiate into the pluripotent epiblast or the primitive endoderm (PrE), marked by the transcription factors NANOG and GATA6, respectively. To investigate the mechanistic regulation of this pro ... Full text Link to item Cite

Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program.

Journal Article Curr Biol · January 21, 2013 In most metazoans, early embryonic development is characterized by rapid mitotic divisions that are controlled by maternal mRNAs and proteins that accumulate during oogenesis. These rapid divisions pause at the midblastula transition (MBT), coinciding with ... Full text Link to item Cite

Short-term integration of Cdc25 dynamics controls mitotic entry during Drosophila gastrulation.

Journal Article Dev Cell · April 17, 2012 Cells commit to mitosis by abruptly activating the mitotic cyclin-Cdk complexes. During Drosophila gastrulation, mitosis is associated with the transcriptional activation of cdc25(string), a phosphatase that activates Cdk1. Here, we demonstrate that the sw ... Full text Link to item Cite

Enhancement of transport selectivity through nano-channels by non-specific competition.

Journal Article PLoS Comput Biol · June 10, 2010 The functioning of living cells requires efficient and selective transport of materials into and out of the cell, and between different cellular compartments. Much of this transport occurs through nano-scale channels that do not require large scale molecul ... Full text Link to item Cite

Enhancement of transport selectivity through nano-channels by non-specific competition.

Journal Article PLoS computational biology · 2010 The functioning of living cells requires efficient and selective transport of materials into and out of the cell, and between different cellular compartments. Much of this transport occurs through nano-scale channels that do not require large scale molecul ... Full text Cite

Daughter-specific transcription factors regulate cell size control in budding yeast.

Journal Article PLoS Biol · October 2009 In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been consid ... Full text Link to item Cite

Positive feedback of G1 cyclins ensures coherent cell cycle entry.

Journal Article Nature · July 17, 2008 In budding yeast, Saccharomyces cerevisiae, the Start checkpoint integrates multiple internal and external signals into an all-or-none decision to enter the cell cycle. Here we show that Start behaves like a switch due to systems-level feedback in the regu ... Full text Link to item Cite

The effects of molecular noise and size control on variability in the budding yeast cell cycle.

Journal Article Nature · August 23, 2007 Molecular noise in gene expression can generate substantial variability in protein concentration. However, its effect on the precision of a natural eukaryotic circuit such as the control of cell cycle remains unclear. We use single-cell imaging of fluoresc ... Full text Link to item Cite

Efficiency, selectivity, and robustness of nucleocytoplasmic transport.

Journal Article PLoS Comput Biol · July 2007 All materials enter or exit the cell nucleus through nuclear pore complexes (NPCs), efficient transport devices that combine high selectivity and throughput. NPC-associated proteins containing phenylalanine-glycine repeats (FG nups) have large, flexible, u ... Full text Link to item Cite

A simulation environment for directional sensing as a phase separation process.

Journal Article Sci STKE · March 20, 2007 The ability of eukaryotic cells to navigate along spatial gradients of extracellular guidance cues is crucial for embryonic development, tissue regeneration, and cancer progression. One proposed model for chemotaxis is a phosphoinositide-based phase separa ... Full text Link to item Cite

Phase separation in eukaryotic directional sensing

Conference · January 1, 2007 Many eukaryotic cell types share the ability to migrate directionally in response to external chemoattractant gradients. The binding of chemoattractants to specific receptors leads to a wide range of biochemical responses that become highly localized as ce ... Full text Cite

Efficiency, selectivity, and robustness of nucleocytoplasmic transport.

Journal Article PLoS computational biology · 2007 All materials enter or exit the cell nucleus through nuclear pore complexes (NPCs), efficient transport devices that combine high selectivity and throughput. NPC-associated proteins containing phenylalanine-glycine repeats (FG nups) have large, flexible, u ... Full text Cite

Role of repulsive factors in vascularization dynamics.

Journal Article Phys Rev E Stat Nonlin Soft Matter Phys · April 2006 Capillary networks are essential in vertebrates to supply tissues with nutrients. Experiments of in vitro capillary formation show that endothelial cells randomly spread on a gel matrix autonomously organize to form vascular networks with a characteristic ... Full text Link to item Cite

A computational model for eukaryotic directional sensing

Conference Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2006 Many eukaryotic cell types share the ability to migrate directionally in response to external chemoattractant gradients. This ability is central in the development of complex organisms, and is the result of billion years of evolution. Cells exposed to shal ... Full text Cite

Diffusion-limited phase separation in eukaryotic chemotaxis.

Journal Article Proc Natl Acad Sci U S A · November 22, 2005 The ability of cells to sense spatial gradients of chemoattractant factors governs the development of complex eukaryotic organisms. Cells exposed to shallow chemoattractant gradients respond with strong accumulation of the enzyme phosphatidylinositol 3-kin ... Full text Link to item Cite

Erratum: Percolation and Burgers' dynamics in a model of capillary formation (Physical Review E (2004) 69 (051910))

Journal Article Physical Review E - Statistical, Nonlinear, and Soft Matter Physics · September 1, 2004 Full text Cite

Percolation and Burgers' dynamics in a model of capillary formation.

Journal Article Phys Rev E Stat Nonlin Soft Matter Phys · May 2004 Capillary networks are essential in vertebrates to supply tissues with nutrients. Experiments of in vitro capillary formation show that cells randomly spread on a gel matrix autonomously organize to form vascular networks. Cells form disconnected networks ... Full text Link to item Cite

Percolation and Burgers' dynamics in a model of capillary formation

Journal Article Physical Review E - Statistical, Nonlinear, and Soft Matter Physics · January 1, 2004 The characterization of model of capillary networks which focus on dynamical properties, fractal properties of patterns and percolative phase transition in biological systems was investigated. The large-scale behavior of system is regulated by initial rand ... Cite

Percolation, morphogenesis, and burgers dynamics in blood vessels formation.

Journal Article Phys Rev Lett · March 21, 2003 Experiments of in vitro formation of blood vessels show that cells randomly spread on a gel matrix autonomously organize to form a connected vascular network. We propose a simple model which reproduces many features of the biological system. We show that b ... Full text Link to item Cite

Percolation, morphogenesis, and burgers dynamics in blood vessels formation

Journal Article Physical Review Letters · March 21, 2003 A theoretical model which turns out to be in good agreement with experimental observations was proposed. It allows one to reproduce well both the observed percolative transition and the typical scale of observed vascular networks. With respect to standard ... Cite