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| Open AccessGeneration of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma
Organs consist of parenchyma and stroma. Nishinakamura and colleagues induce renal stromal progenitors from mouse pluripotent stem cells (PSCs), and generate completely PSC-derived organoids that reproduce complex kidney structure.
- Shunsuke Tanigawa
- , Etsuko Tanaka
- & Ryuichi Nishinakamura
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| Open AccessIntegration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development
The molecular basis and gene regulatory networks driving pharyngeal endoderm development remain poorly understood. Here the authors report single cell transcriptomic and chromatin landscapes to delineate regulatory programs driving this process and to define the immunodeficiency-associated developmental defects resulting from Foxn1 dysfunction.
- Margaret E. Magaletta
- , Macrina Lobo
- & René Maehr
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| Open AccessSequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors
Enhancers for endodermal organs are primed at the chromatin level prior to lineage induction by FOXA pioneer transcription factors; how pervasive this is, is not well known. Here the authors show that only a small subset of organ-specific enhancers are bound and primed by FOXA prior to lineage induction, whereas the majority do not undergo chromatin priming and engage FOXA upon lineage induction.
- Ryan J. Geusz
- , Allen Wang
- & Maike Sander
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Article
| Open AccessAsymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
Morphogens disperse to pattern tissues and control their growth during development, allowing for the specification of multiple fates across space. Here the authors block dispersal of a morphogen Dpp (BMP2/4) and show that the requirement for Dpp dispersal is much lower than previously thought.
- Shinya Matsuda
- , Jonas V. Schaefer
- & Markus Affolter
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| Open AccessProgenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis
The cessation of nephrogenesis determines nephron endowments in mammals. Here the authors show that differential translation of Wnt antagonists versus agonists determines the tipping point from self-renewal to differentiation of nephron progenitors during nephrogenesis, using mutant mice with elevated nephron numbers.
- Alison E. Jarmas
- , Eric W. Brunskill
- & Raphael Kopan
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| Open AccessAnalysis of gene network bifurcation during optic cup morphogenesis in zebrafish
The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.
- Lorena Buono
- , Jorge Corbacho
- & Juan-Ramón Martínez-Morales
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Article
| Open AccessUnexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning
The dogma is that limb muscle cells originate from somite, while connective tissue fibroblasts derive from lateral plate mesoderm. Here the authors identify a fibroblast population that undergoes myoblast conversion in response to BMP and contributes nuclei to myotubes at the myotendinous junction.
- Joana Esteves de Lima
- , Cédrine Blavet
- & Delphine Duprez
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| Open AccessA 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion
From single-cell transcriptome analyses to defining culture media for spheroids, the authors provide a census of information to understand the development of human pancreatic progenitors. This approach identifies signalling pathways (EGF and FGF) regulating progenitor proliferation.
- Carla A. Gonçalves
- , Michael Larsen
- & Anne Grapin-Botton
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Article
| Open AccessA coordinated progression of progenitor cell states initiates urinary tract development
Nephric duct (ND)-derived ureteric buds (UB) form the kidney collecting duct system, while ureteric tips promote nephron formation. Here the authors use single-cell RNA-seq and introduce Cluster RNA-seq to identify four progenitor populations in developing ND/UB regulated by the transcription factors Tfap2a/b and Gata3.
- Oraly Sanchez-Ferras
- , Alain Pacis
- & Maxime Bouchard
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Article
| Open AccessDifferential chromatin binding of the lung lineage transcription factor NKX2-1 resolves opposing murine alveolar cell fates in vivo
How transcription factors regulate cell fates in native tissues is unclear. Here, the authors report that differential chromatin binding of NKX2-1 determines opposing alveolar cell fates in the murine lung, showing loss of YAP/TAZ directs NKX2-1 to alternative binding sites leading to cell fate conversion.
- Danielle R. Little
- , Anne M. Lynch
- & Jichao Chen
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Article
| Open AccessMyofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle
Mitochondria produce high amounts of ATP to power myosin motors and sustained muscle contraction. Here, the authors show that during development, muscles coordinate the morphogenesis of their myofibrils directly with their mitochondria to optimize both for the physiological needs of each muscle-type.
- Jerome Avellaneda
- , Clement Rodier
- & Frank Schnorrer
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Article
| Open AccessSpatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis
Using single-cell and spatial transcriptomics in chicken hearts, here, the authors generate a census of cellular interactions from early to late four-chambered heart stage, identifying a distinct epicardial-mesenchymal cell population with a migratory phenotype.
- Madhav Mantri
- , Gaetano J. Scuderi
- & Iwijn De Vlaminck
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Article
| Open AccessTGFβ signalling acts as a molecular brake of myoblast fusion
Fusion of myoblasts is essential for muscle development and repair, but the molecular mechanism underlying this process remains unclear. Here, the authors show, using chicken embryos as a model, that TGFβ signalling inhibits fusion via a receptor complementation mechanism, and indicate the involvement of endocytic degradation of activated receptors in modulation of this process.
- Julie Melendez
- , Daniel Sieiro
- & Christophe Marcelle
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| Open AccessTGFβ signaling curbs cell fusion and muscle regeneration
The fusion of muscle progenitor cells to form syncytial myofibers is required for skeletal muscle development and regeneration. Here, the authors describe a novel and specific molecular regulation of muscle cell fusion driven by transforming growth factor beta (TGFβ) signaling.
- Francesco Girardi
- , Anissa Taleb
- & Fabien Le Grand
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Article
| Open AccessSingle-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers
Mammalian skeletal muscle is composed of multinucleated myofibers, containing hundreds of nuclei that coordinate cellular function. Here, the authors show that single-nucleus RNA-sequencing reveals rare and emergent myonuclear populations, and uncovers dynamic transcriptional heterogeneity in development and aging.
- Michael J. Petrany
- , Casey O. Swoboda
- & Douglas P. Millay
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Article
| Open AccessSingle-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells
The transcriptional programs of nuclei in the muscle syncytium were assumed to be homogenous except at the neuromuscular and myotendinous junctions. Here, using single-nucleus transcriptomics, the authors reveal a previously unrecognized diversity and dynamics of myonuclear transcriptional programs.
- Minchul Kim
- , Vedran Franke
- & Carmen Birchmeier
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Article
| Open AccessSTRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells
STRAP (serine threonine kinase receptor-associated protein) promotes tumorigenicity. Here the authors report that STRAP associates with spliceosome and regulates alternative splicing during embryonic stem cell lineage commitment and early mouse embryo organogenesis.
- Lin Jin
- , Yunjia Chen
- & Pran K. Datta
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Article
| Open AccessTracing the cellular basis of islet specification in mouse pancreas
The cellular basis of islet morphogenesis and fate allocation remain unclear. Here, the authors use a R26-CreER-R26R-Confetti mouse line to follow quantitatively the clonal dynamics of islet formation showing how, during the secondary transition, islet progenitors amplify through rounds of stochastic cell division before becoming restricted to α and β cell sublineages.
- Magdalena K. Sznurkowska
- , Edouard Hannezo
- & Benjamin D. Simons
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| Open AccessDental cell type atlas reveals stem and differentiated cell types in mouse and human teeth
Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.
- Jan Krivanek
- , Ruslan A. Soldatov
- & Igor Adameyko
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| Open AccessSingle cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis
The fetal murine foregut develops into visceral organs via interactions between the mesoderm and endoderm, but how is unclear. Here, the authors use single cell RNAseq to show a diversity in organ specific splanchnic mesoderm cell-types, infer a signalling network governing organogenesis and use this to differentiate human pluripotent stem cells.
- Lu Han
- , Praneet Chaturvedi
- & Aaron M. Zorn
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Article
| Open AccessBidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells
How murine tracheal mesenchyme is specified during development is unclear. Here, the authors show a Wnt pathway target, Tbx4, is needed but this is regulated by Wnt signals from neighbouring tracheal epithelial cells, and take advantage of this knowledge to generate tracheal cartilage and smooth muscle on dish from mouse and human embryonic stem cells.
- Keishi Kishimoto
- , Kana T. Furukawa
- & Mitsuru Morimoto
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| Open AccessDynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders
How the epigenomic landscape linked to transcription regulates human embryonic development is unclear. Here, the authors analyse the dynamics of H3K27Ac, H3K4me3 and H3K27me3 during the period when organs first assemble as a platform for understanding noncoding developmental disorders.
- Dave T. Gerrard
- , Andrew A. Berry
- & Neil A. Hanley
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| Open AccessDevelopmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
Brain organoids are important tools to study early development and disease but little is known of their network activity and plasticity. Here the authors generate iPSC-derived neuronal organoids that display early network formation and maturation with evidence for a GABA polarity switch and long-term potentiation.
- Maria-Patapia Zafeiriou
- , Guobin Bao
- & Wolfram-Hubertus Zimmermann
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| Open AccessEpithelial invagination by a vertical telescoping cell movement in mammalian salivary glands and teeth
Mechanisms that regulate epithelial bending mainly link to cell shape changes, for example, the formation of wedge shaped cells. Here, the authors identify a different cell behaviour in the salivary glands and teeth where initial invagination arises by a coordinated vertical cell movement.
- Jingjing Li
- , Andrew D. Economou
- & Jeremy B. A. Green
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Article
| Open AccessCytokinetic bridge triggers de novo lumen formation in vivo
De novo lumen formation during vertebrate left–right organizer development is required for body axis establishment. Here the authors utilize zebrafish to demonstrate that the position and cleavage of the cytokinetic bridge in dividing left-right organizer cells dictates tissue morphogenesis.
- L. I. Rathbun
- , E. G. Colicino
- & H. Hehnly
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Article
| Open AccessIdentification of a Zeb1 expressing basal stem cell subpopulation in the prostate
Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.
- Xue Wang
- , Haibo Xu
- & Helen He Zhu
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Article
| Open AccessYAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells
Fibroblastic reticular cells (FRC) are important for lymph node (LN) structure and function. Here the authors show that the YAP/TAZ complex downstream of Hippo signalling regulates FRC commitment and maturation, with YAP/TAZ deficiency impairing FRC differentiation, while hyperactivation of YAZ/TAZ inducing myofibroblastic FRCs and LN fibrosis.
- Sung Yong Choi
- , Hosung Bae
- & Gou Young Koh
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| Open AccessSufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals
Dynamic mesenchyme derived signals are known to direct proper organ formation and cell specification in vivo. Here the authors show in mice that mesenchyme derived Hedgehog and Wnt instruct the formation of the pancreas and beta cells, and that Wnt inhibition promotes beta cell formation from human pluripotent cells.
- Theodora Yung
- , Frankie Poon
- & Tae-Hee Kim
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Article
| Open AccessPparg promotes differentiation and regulates mitochondrial gene expression in bladder epithelial cells
The nuclear receptor Pparg regulates urothelial differentiation in vitro but its role in healthy urothelium is unclear. Here, the authors show that PPAR gamma mediates urothelial development during both homeostasis (via mitochondrial function) and following infection, via an inflammatory response.
- Chang Liu
- , Tiffany Tate
- & Cathy Lee Mendelsohn
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Article
| Open AccessSelf-organized formation of developing appendages from murine pluripotent stem cells
Organoid technology has been applied to model many types of organs in vitro, although structures containing multiple germ layers, such as limb buds, have not been generated. Here, the authors induce limb bud-like tissues from mouse ESCs that can be functionally integrated after transplantation.
- Shunsuke Mori
- , Eriko Sakakura
- & Mototsugu Eiraku
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Article
| Open AccessRegulatory pathways governing murine coronary vessel formation are dysregulated in the injured adult heart
How coronary vessels develop and respond to injury is not fully understood. Here, the authors use murine enhancer:reporter models to identify three transcriptional pathways active in different parts of coronary vasculature. These also contribute to neovascularization in the injured neonatal, but not adult, heart.
- Sophie Payne
- , Mala Gunadasa-Rohling
- & Sarah De Val
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Article
| Open AccessEvidence against tetrapod-wide digit identities and for a limited frame shift in bird wings
The homology of digits across amniotes is debated. Here, the authors compare the developmental transcriptomes of digits across five divergent amniotes and show high evolutionary dynamism in expression profiles, with conservation of a distinct developmental identity only in the anterior-most digit.
- Thomas A. Stewart
- , Cong Liang
- & Günter P. Wagner
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| Open AccessLoss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes
Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.
- Rodrigo Diéguez-Hurtado
- , Katsuhiro Kato
- & Ralf H. Adams
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Article
| Open AccessSpinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2
Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm cells.
- Evanthia Nikolopoulou
- , Caroline S. Hirst
- & Nicholas D. E. Greene
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Article
| Open AccessBlimp1+ cells generate functional mouse sebaceous gland organoids in vitro
The sebaceous gland (SG) has been proposed to be replenished by pools of cells, including a population in the SG base, marked by Blimp1. Here, the authors show that Blimp1+ cells can establish an organoid model of the SG, which is regulated by c-Myc and can recapitulate the early stages of acne vulgaris.
- Alona Feldman
- , Dzmitry Mukha
- & Yaron Fuchs
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Article
| Open AccessOrigin and differentiation trajectories of fibroblastic reticular cells in the splenic white pulp
The white pulp of spleen is an important immune structure dynamically modulated during development and immune responses. Here the authors define, using multi-color lineage tracing and single-cell transcriptome analysis, the subset distribution and differentiation trajectory of fibroblastic reticular cells to serve structural insights for splenic white pulps.
- Hung-Wei Cheng
- , Lucas Onder
- & Burkhard Ludewig
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Article
| Open AccessA MST1–FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis
Angiogenesis is driven by the directed migration of tip endothelial cells towards hypoxic tissues. Here, Kim et al. show that the generation of reactive oxygen species in endothelial cells upon hypoxia activates MST1, which subsequently promotes the nuclear translocation of FOXO1, and thus activates a pro-migratory transcriptional programme in endothelial tip cells.
- Yoo Hyung Kim
- , Jeongwoon Choi
- & Gou Young Koh
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Article
| Open Accesstmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.
- Aaron M. Savage
- , Sathishkumar Kurusamy
- & Robert N. Wilkinson
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Article
| Open AccessVenous identity requires BMP signalling through ALK3
The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.
- Alice Neal
- , Svanhild Nornes
- & Sarah De Val
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Article
| Open AccessTissue engineering of human hair follicles using a biomimetic developmental approach
Human skin constructs hold potential for regenerative medicine, but the incorporation of hair follicles into such constructs is a challenge. Here, the authors use 3D printed molds to pattern hair follicle cell types in a physiological organization, and achieve human hair growth on the back of a mouse.
- Hasan Erbil Abaci
- , Abigail Coffman
- & Angela M. Christiano
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Article
| Open AccessA time-resolved multi-omic atlas of the developing mouse stomach
The mammalian stomach is a complex organ with diverse roles in health and disease. Here, the authors integrate proteomics and transcriptomics to analyze the mouse stomach at 15 time points during development, providing molecular level insights into system-wide developmental changes.
- Xianju Li
- , Chunchao Zhang
- & Jun Qin
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Article
| Open AccessA perivascular niche for multipotent progenitors in the fetal testis
Leydig cells are steroidogenic cells in the testes and produce the androgens required for male development and spermatogenesis. Here the authors show that a multipotent progenitor population producing Leydig cells, pericytes and smooth muscle cells is maintained in a perivascular niche within the mouse fetal testis.
- Deepti L. Kumar
- & Tony DeFalco
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Article
| Open AccessGeneration of orthotopically functional salivary gland from embryonic stem cells
Functional salivary glands have not been generated from embryonic stem cells (mESCs) to date. Here the authors demonstrate directed in vitro differentiation of mESCs to oral ectoderm and salivary gland rudiments that form mature, functional salivary glands after orthotopic transplantation.
- Junichi Tanaka
- , Miho Ogawa
- & Kenji Mishima
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Article
| Open AccessNCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy
Pericytes are perivascular cells that regulate blood vessel formation and function. Here Dubrac et al. show that pericyte recruitment contributes to pathological neovascularisation in a mouse model of ischemic retinopathy, and that this depends on the regulation of PDGF-B signaling by NCK adaptor proteins.
- Alexandre Dubrac
- , Steffen E. Künzel
- & Anne Eichmann
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Article
| Open AccessSynchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus
Tracheal development arises due to tube morphogenesis but how this is regulated is unclear. Here, the authors identify polarization of smooth muscle progenitors as controlling murine tracheal development, activating noncanonical Wnt signaling followed by subepithelial morphogenesis and ring cartilage development.
- Keishi Kishimoto
- , Masaru Tamura
- & Mitsuru Morimoto
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Article
| Open AccessContinuous addition of progenitors forms the cardiac ventricle in zebrafish
Late-differentiating second heart field progenitors contribute to atrium, ventricle, and outflow tract in the zebrafish heart but how remains unclear. Here, the authors image heart formation in transgenics based on the cardiopharyngeal gene tbx1 and show that progenitors are continuously added.
- Anastasia Felker
- , Karin D. Prummel
- & Christian Mosimann
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Article
| Open AccessThe AFF-1 exoplasmic fusogen is required for endocytic scission and seamless tube elongation
Membrane fusion and fission events at exoplasmic membrane surfaces are not well understood. Here the authors show that the C. elegans cell–cell fusogen AFF-1 is required for endocytic scission and apically-directed membrane trafficking during the development of a unicellular tube.
- Fabien Soulavie
- , David H. Hall
- & Meera V. Sundaram
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Article
| Open AccessMatrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
Mechanical cues are known to influence endothelial cell behavior. Here Frye et al. show that lymphatic endothelial cell progenitors experience varying degrees of matrix stiffness during development, and that matrix stiffness regulates GATA2 expression to drive lymphatic vessel formation.
- Maike Frye
- , Andrea Taddei
- & Taija Mäkinen
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Article
| Open AccessHeterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms
VEGF-C is a key regulator of lymphatic development. Here, Zhang et al. show that while complete loss of its receptor VEGFR3 results in vessel hypoplasia, mosaic loss of VEGFR3 leads to hyperplasia through induction of cell proliferation in neighboringnon-targeted cells, uncovering cell- and non-cell-autonomous roles for VEGFR3 during lymphatic vessel growth.
- Yan Zhang
- , Maria H. Ulvmar
- & Taija Mäkinen