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Terry H. Lechler

Professor in Dermatology
Dermatology
Duke Box 3709, Durham, NC 27710
310 Nanaline Duke Bldg, Durham, NC 27710

Selected Publications


Mesenchymal cell contractility regulates villus morphogenesis and intestinal architecture.

Journal Article Dev Biol · March 2025 The large absorptive surface area of the small intestine is imparted by finger-like projections called villi. Villi formation is instructed by stromal-derived clusters of cells which have been proposed to induce epithelial bending through actomyosin contra ... Full text Link to item Cite

Compartment specific responses to contractility in the small intestinal epithelium.

Journal Article PLoS Genet · March 2024 Tissues are subject to multiple mechanical inputs at the cellular level that influence their overall shape and function. In the small intestine, actomyosin contractility can be induced by many physiological and pathological inputs. However, we have little ... Full text Link to item Cite

Polarity in skin development and cancer.

Chapter · 2023 The epidermis is a stratified squamous epithelium that forms the outermost layer of the skin. Its primary function is to act as a barrier, keeping pathogens and toxins out and moisture in. This physiological role has necessitated major differences in the o ... Full text Link to item Cite

Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut.

Journal Article Development · December 1, 2022 There are fundamental differences in how neonatal and adult intestines absorb nutrients. In adults, macromolecules are broken down into simpler molecular components in the lumen of the small intestine, then absorbed. In contrast, neonates are thought to re ... Full text Link to item Cite

Hair follicle stem cells feel the pressure.

Journal Article Cell Stem Cell · January 6, 2022 The number of hair follicle stem cells decreases during aging and in hair-loss disorders, such as alopecia. In this issue of Cell Stem Cell, Xie et al. (2021) discover that the hair shaft serves as a physical niche component for the preservation of hair fo ... Full text Link to item Cite

KIF18B is a cell type-specific regulator of spindle orientation in the epidermis.

Journal Article Mol Biol Cell · November 1, 2021 Proper spindle orientation is required for asymmetric cell division and the establishment of complex tissue architecture. In the developing epidermis, spindle orientation requires a conserved cortical protein complex of LGN/NuMA/dynein-dynactin. However, h ... Full text Link to item Cite

Spindle positioning and its impact on vertebrate tissue architecture and cell fate.

Journal Article Nature reviews. Molecular cell biology · October 2021 In multicellular systems, oriented cell divisions are essential for morphogenesis and homeostasis as they determine the position of daughter cells within the tissue and also, in many cases, their fate. Early studies in invertebrates led to the identificati ... Full text Cite

Roles for Ndel1 in keratin organization and desmosome function.

Journal Article Mol Biol Cell · October 1, 2021 Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell ... Full text Link to item Cite

Differentiated Daughter Cells Regulate Stem Cell Proliferation and Fate through Intra-tissue Tension.

Journal Article Cell Stem Cell · March 4, 2021 Basal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal p ... Full text Link to item Cite

Roles for microtubules in the proliferative and differentiated cells of stratified epithelia.

Journal Article Curr Opin Cell Biol · February 2021 While microtubule dynamics and organization have been extensively studied invitro, both biochemically and in cultured cells, recent work has begun to extend this into tissues ex vivo and organisms in vivo. Advances in genetic tools and imaging technology h ... Full text Link to item Cite

RYK-mediated filopodial pathfinding facilitates midgut elongation.

Journal Article Development (Cambridge, England) · October 2020 Between embryonic days 10.5 and 14.5, active proliferation drives rapid elongation of the murine midgut epithelial tube. Within this pseudostratified epithelium, nuclei synthesize DNA near the basal surface and move apically to divide. After mitosis, the m ... Full text Cite

Proteomic analysis of desmosomes reveals novel components required for epidermal integrity.

Journal Article Mol Biol Cell · May 15, 2020 Desmosomes are cell-cell adhesions necessary for the maintenance of tissue integrity in the skin and heart. While the core components of desmosomes have been identified, peripheral components that modulate canonical or noncanonical desmosome functions stil ... Full text Link to item Cite

Epidermal structure and differentiation.

Journal Article Curr Biol · February 24, 2020 In this Primer, Moreci and Lechler follow the lifetime of an epidermal cell from its birth to its ultimate death, and detail how this journey is necessary for epidermal function. ... Full text Link to item Cite

Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.

Journal Article Dev Cell · October 7, 2019 The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is ... Full text Link to item Cite

Regulated spindle orientation buffers tissue growth in the epidermis.

Journal Article Elife · October 2, 2019 Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell div ... Full text Open Access Link to item Cite

Cellular Dynamics Driving Elongation of the Gut.

Journal Article Dev Cell · July 16, 2018 During embryonic development, the midgut needs to undergo extensive elongation to form the small intestine. In this issue of Development Cell, Wang et. al. (2018) explore the cell dynamics of this tissue and find that regulated re-integration of cells into ... Full text Link to item Cite

Genetically induced microtubule disruption in the mouse intestine impairs intracellular organization and transport.

Journal Article Mol Biol Cell · July 1, 2018 In most differentiated cells, microtubules reorganize into noncentrosomal arrays that are cell-type specific. In the columnar absorptive enterocytes of the intestine, microtubules form polarized apical-basal arrays that have been proposed to play multiple ... Full text Link to item Cite

Morphogenesis and Compartmentalization of the Intestinal Crypt.

Journal Article Dev Cell · April 23, 2018 The adult mammalian intestine is composed of two connected structures, the absorptive villi and the crypts, which house progenitor cells. Mouse crypts develop postnatally and are the architectural unit of the stem cell niche, yet the pathways that drive th ... Full text Link to item Cite

A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis.

Journal Article Elife · September 4, 2017 The physiological functions of microtubules (MTs) are poorly understood in many differentiated cell types. We developed a genetic toolkit to study MT dynamics and function in diverse cells. Using TRE-EB1-GFP mice, we found that MT dynamics are strongly sup ... Full text Link to item Cite

Microtubule organization, dynamics and functions in differentiated cells.

Journal Article Development · September 1, 2017 Over the past several decades, numerous studies have greatly expanded our knowledge about how microtubule organization and dynamics are controlled in cultured cells in vitro However, our understanding of microtubule dynamics and functions in vivo, in diffe ... Full text Link to item Cite

Divergent regulation of functionally distinct γ-tubulin complexes during differentiation.

Journal Article J Cell Biol · June 20, 2016 Differentiation induces the formation of noncentrosomal microtubule arrays in diverse tissues. The formation of these arrays requires loss of microtubule-organizing activity (MTOC) at the centrosome, but the mechanisms regulating this transition remain lar ... Full text Link to item Cite

FRA1 promotes squamous cell carcinoma growth and metastasis through distinct AKT and c-Jun dependent mechanisms.

Journal Article Oncotarget · June 7, 2016 FRA1 (Fos-like antigen 1) is highly expressed in many epithelial cancers including squamous cell carcinoma of the skin (cSCC) and head and neck (HNSCC). However, the functional importance and the mechanisms mediating FRA1 function in these cancers are not ... Full text Open Access Link to item Cite

NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures.

Journal Article Elife · January 14, 2016 Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical ... Full text Link to item Cite

Studying cell biology in the skin.

Journal Article Mol Biol Cell · November 15, 2015 Advances in cell biology have often been driven by studies in diverse organisms and cell types. Although there are technical reasons for why different cell types are used, there are also important physiological reasons. For example, ultrastructural studies ... Full text Link to item Cite

The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine.

Journal Article Mol Biol Cell · June 1, 2015 The Arp2/3 complex is the only known nucleator of branched F-actin filaments. Work in cultured cells has established a wide array of functions for this complex in controlling cell migration, shape, and adhesion. However, loss of Arp2/3 complex function in ... Full text Link to item Cite

Cell adhesion in epidermal development and barrier formation.

Journal Article Curr Top Dev Biol · 2015 Cell-cell adhesions are necessary for structural integrity and barrier formation of the epidermis. Here, we discuss insights from genetic and cell biological studies into the roles of individual cell-cell junctions and their composite proteins in regulatin ... Full text Link to item Cite

Arp2/3 complex function in the epidermis

Journal Article Tissue Barriers · October 30, 2014 An exciting frontier in biology is understanding the functions of basic cell biological machinery in complex tissues. This approach is expected to uncover novel modes of regulation as well as reveal how core machinery is repurposed by different tissues to ... Full text Cite

Developmental stratification of the mammary epithelium occurs through symmetry-breaking vertical divisions of apically positioned luminal cells.

Journal Article Development · March 2014 Mammary ducts are elongated during development by stratified epithelial structures, known as terminal end buds (TEBs). TEBs exhibit reduced apicobasal polarity and extensive proliferation. A major unanswered question concerns the mechanism by which the sim ... Full text Link to item Cite

Cell-cell adhesions and cell contractility are upregulated upon desmosome disruption.

Journal Article PLoS One · 2014 Desmosomes are perturbed in a number of disease states - including genetic disorders, autoimmune and bacterial diseases. Here, we report unexpected changes in other cell-cell adhesion structures upon loss of desmosome function. We found that perturbation o ... Full text Link to item Cite

NuMA localization, stability, and function in spindle orientation involve 4.1 and Cdk1 interactions.

Journal Article Mol Biol Cell · December 2013 The epidermis is a multilayered epithelium that requires asymmetric divisions for stratification. A conserved cortical protein complex, including LGN, nuclear mitotic apparatus (NuMA), and dynein/dynactin, plays a key role in establishing proper spindle or ... Full text Link to item Cite

Actin-related protein2/3 complex regulates tight junctions and terminal differentiation to promote epidermal barrier formation.

Journal Article Proc Natl Acad Sci U S A · October 1, 2013 The epidermis provides an essential seal from the external environment and retains fluids within the body. To form an effective barrier, cells in the epidermis must form tight junctions and terminally differentiate into cornified envelopes. Here, we demons ... Full text Link to item Cite

beta-Catenin protects the epidermis from mechanical stresses.

Journal Article J Cell Biol · July 8, 2013 Many tissues in our body experience mechanical stresses caused by both internal and external forces. The skin, for example, must tolerate diverse mechanical insults. In this paper, we report a role for β-catenin in providing stability to epithelia under st ... Full text Link to item Cite

FRAP analysis reveals stabilization of adhesion structures in the epidermis compared to cultured keratinocytes.

Journal Article PLoS One · 2013 Proper development and tissue maintenance requires cell-cell adhesion structures, which serve diverse and crucial roles in tissue morphogenesis. Epithelial tissues have three main types of cell-cell junctions: tight junctions, which play a major role in ba ... Full text Link to item Cite

Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation.

Journal Article J Cell Biol · October 29, 2012 During differentiation, many cells reorganize their microtubule cytoskeleton into noncentrosomal arrays. Although these microtubules are likely organized to meet the physiological roles of their tissues, their functions in most cell types remain unexplored ... Full text Link to item Cite

Polarity and stratification of the epidermis.

Journal Article Semin Cell Dev Biol · October 2012 Polarity is a fundamental property of epithelial cells. In this review, we discuss our current knowledge of the polarity of a stratified epithelium, the epidermis, focusing on similarities and differences with simple epithelial models. We highlight how the ... Full text Link to item Cite

Desmoplakin controls microvilli length but not cell adhesion or keratin organization in the intestinal epithelium.

Journal Article Mol Biol Cell · March 2012 Maintaining proper cell-cell adhesion in the intestine is essential for tissue homeostasis and barrier function. This adhesion is thought to be mediated by cell adhesion structures, including tight junctions, adherens junctions, and desmosomes, which conce ... Full text Link to item Cite

Adherens junctions and stem cells.

Journal Article Subcell Biochem · 2012 The specification, maintenance, division and differentiation of stem cells are integral to the development and homeostasis of many tissues. These stem cells often live in specialized anatomical areas, called niches. While niches can be complex, most involv ... Full text Link to item Cite

Asymmetric cell divisions in the epidermis.

Journal Article Int Rev Cell Mol Biol · 2012 Generation of three-dimensional tissues with distinct cell types is required for the development of all organs. On its own, mitotic spindle orientation allows tissues to change in length or shape. In combination with intrinsic or extrinsic cues, this can a ... Full text Link to item Cite

Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis.

Journal Article J Cell Biol · August 22, 2011 Desmosomes are cell-cell adhesion structures that integrate cytoskeletal networks. In addition to binding intermediate filaments, the desmosomal protein desmoplakin (DP) regulates microtubule reorganization in the epidermis. In this paper, we identify a sp ... Full text Link to item Cite

Regulation of asymmetric cell division in the epidermis.

Journal Article Cell Div · June 6, 2011 For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions. Progenitor cells in the developing epidermis undergo bo ... Full text Link to item Cite

Robust control of mitotic spindle orientation in the developing epidermis.

Journal Article J Cell Biol · November 29, 2010 Progenitor cells must balance self-amplification and production of differentiated progeny during development and homeostasis. In the epidermis, progenitors divide symmetrically to increase surface area and asymmetrically to promote stratification. In this ... Full text Link to item Cite

Dissecting cell adhesion cross-talk with micropatterns.

Journal Article Proc Natl Acad Sci U S A · July 27, 2010 Full text Link to item Cite

Limiting lumens: a new role for Cdc42.

Journal Article J Cell Biol · November 17, 2008 The formation of a single lumen is a necessary step in the formation of biological tubes. Different tissues have developed diverse ways to form their lumens. In this issue, Jaffe et al. (Jaffe, A.B., N. Kaji, J. Durgan, and A. Hall. 2008. J. Cell Biol. 183 ... Full text Link to item Cite

Terry Lechler: the cytoskeleton is skin deep. Interview by Nicole LeBrasseur.

Journal Article J Cell Biol · August 13, 2007 If form is function, Terry Lechler thinks scientists should know more about how cells acquire their form. That's one reason he studies the cytoskeleton. ... Full text Link to item Cite

Desmoplakin: an unexpected regulator of microtubule organization in the epidermis.

Journal Article J Cell Biol · January 15, 2007 Despite their importance in cell shape and polarity generation, the organization of microtubules in differentiated cells and tissues remains relatively unexplored in mammals. We generated transgenic mice in which the epidermis expresses a fluorescently lab ... Full text Link to item Cite

Asymmetric cell divisions promote stratification and differentiation of mammalian skin.

Journal Article Nature · September 8, 2005 The epidermis is a stratified squamous epithelium forming the barrier that excludes harmful microbes and retains body fluids. To perform these functions, proliferative basal cells in the innermost layer periodically detach from an underlying basement membr ... Full text Link to item Cite

Coordinating cytoskeletal tracks to polarize cellular movements.

Journal Article J Cell Biol · October 25, 2004 For many years after the discovery of actin filaments and microtubules, it was widely assumed that their polymerization, organization, and functions were largely distinct. However, in recent years it has become increasingly apparent that coordinated intera ... Full text Link to item Cite

Conditional targeting of E-cadherin in skin: insights into hyperproliferative and degenerative responses.

Journal Article Proc Natl Acad Sci U S A · January 13, 2004 Loss of E-cadherin has been associated with human cancers, and yet in the early mouse embryo and the lactating mammary gland, the E-cadherin null state results in tissue dysfunction and cell death. Here we targeted loss of E-cadherin in skin epithelium. Th ... Full text Link to item Cite

Rapid de-localization of actin leading edge components with BDM treatment.

Journal Article BMC Cell Biol · June 3, 2003 BACKGROUND: 2,3-butanedione monoxime (BDM) has been widely used as a non-muscle myosin inhibitor to investigate the role of non-muscle myosinII in the process of actin retrograde flow and other actin cytoskeletal processes. Recent reports show that BDM doe ... Full text Link to item Cite

Saccharomyces cerevisiae Bzz1p is implicated with type I myosins in actin patch polarization and is able to recruit actin-polymerizing machinery in vitro.

Journal Article Mol Cell Biol · November 2002 In Saccharomyces cerevisiae, the WASP (Wiskott-Aldrich syndrome protein) homologue Las17p (also called Bee1p) is an important component of cortical actin patches. Las17p is part of a high-molecular-weight protein complex that regulates Arp2/3 complex-depen ... Full text Link to item Cite

A two-tiered mechanism by which Cdc42 controls the localization and activation of an Arp2/3-activating motor complex in yeast.

Journal Article J Cell Biol · October 15, 2001 The establishment of cell polarity in budding yeast involves assembly of actin filaments at specified cortical domains. Elucidation of the underlying mechanism requires an understanding of the machinery that controls actin polymerization and how this machi ... Full text Link to item Cite

Direct involvement of yeast type I myosins in Cdc42-dependent actin polymerization.

Journal Article J Cell Biol · January 24, 2000 The generation of cortical actin filaments is necessary for processes such as cell motility and cell polarization. Several recent studies have demonstrated that Wiskott-Aldrich syndrome protein (WASP) family proteins and the actin-related protein (Arp) 2/3 ... Full text Link to item Cite

Activation of the yeast Arp2/3 complex by Bee1p, a WASP-family protein.

Journal Article Curr Biol · May 6, 1999 The Arp2/3 complex is a highly conserved cytoskeletal component that has been implicated in the nucleation of actin filament assembly. Purified Arp2/3 complex has a low intrinsic actin nucleation activity, leading to the hypothesis that an unidentified cel ... Full text Link to item Cite

Identification, chromosomal mapping and tissue-specific expression of hREV3 encoding a putative human DNA polymerase zeta.

Journal Article Carcinogenesis · May 1998 The Saccharomyces cerevisiae REV3 gene encodes the catalytic subunit of a non-essential DNA polymerase zeta, which is required for mutagenesis. The rev3 mutants significantly reduce both spontaneous and DNA damage-induced mutation rates. We have identified ... Full text Link to item Cite

In vitro reconstitution of cortical actin assembly sites in budding yeast.

Journal Article J Cell Biol · July 14, 1997 We have developed a biochemical approach for identifying the components of cortical actin assembly sites in polarized yeast cells, based on a permeabilized cell assay that we established for actin assembly in vitro. Previous analysis indicated that an acti ... Full text Link to item Cite

(Aryloxy)aryl semicarbazones and related compounds: a novel class of anticonvulsant agents possessing high activity in the maximal electroshock screen.

Journal Article J Med Chem · September 27, 1996 A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated for anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylene ... Full text Link to item Cite

Oxidized LDL as mediators of atherogenesis

Journal Article Herz Kreislauf · September 26, 1996 The formation of atherosclerotic plaques as a consequence of lipid accumulation in arterial walls apperently is not only caused by a complete removal of endothelial cells of the intima but is also observable under intact endothel. The active storage proces ... Cite