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Michele Marass, Arica Beisaw, Claudia Gerri, Francesca Luzzani, Nana Fukuda, Stefan Günther, Carsten Kuenne, Sven Reischauer, Didier Y R Stainier
The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification remains incomplete. Zebrafish cloche/npas4l mutants have been used broadly as an avascular model, but little is known about the molecular mechanisms of action of the Npas4l transcription factor. Here, to identify its direct and indirect target genes, we combined complementary genome-wide approaches including transcriptome analyses and chromatin immunoprecipitation...
May 16, 2019: Development
Arun Sampathkumar, Alexis Peaucelle, Miki Fujita, Christoph Schuster, Staffan Persson, Geoffrey O Wasteneys, Elliot M Meyerowitz
How organisms attain their specific shapes and modify their growth patterns in response to environmental and chemical signals has been the subject of many investigations. Plant cells are at high turgor pressure, and are surrounded by a rigid yet flexible cell wall, which is the primary determinant of plant growth and morphogenesis. Cellulose microfibrils, synthesized by plasma membrane-localized cellulose synthase complexes, are major tension-bearing components of the cell wall that mediate directional growth...
May 10, 2019: Development
V Patil, H I McDermott, T McAllister, M Cummins, J C Silva, E Mollison, R Meikle, J Morris, P E Hedley, R Waugh, C Dockter, M Hansson, S M McKim
Many plants dramatically elongate their stems during flowering, yet how this response is coordinated with the reproductive phase is unclear. We demonstrate that microRNA (miRNA) control of APETALA2 ( AP2 ) is required for rapid, complete elongation of stem internodes in barley, especially of the final 'peduncle' internode directly underneath the inflorescence. Disrupted miR172 -targeting of AP2 in the Zeo1.b barley mutant caused lower mitotic activity, delayed growth dynamics and premature lignification in the peduncle leading to fewer and shorter cells...
May 10, 2019: Development
Robert Reinhardt, Fabiana Gullotta, Gretel Nusspaumer, Erkan Ünal, Robert Ivanek, Aimée Zuniga, Rolf Zeller
The key molecular interactions governing vertebrate limb bud development are a paradigm to study the mechanisms controlling progenitor cell proliferation and specification during vertebrate organogenesis. However, little is known about the cellular heterogeneity of the mesenchymal progenitors in early limb buds that ultimately contribute to the chondrogenic condensations prefiguring the skeleton. We combined flow cytometric and transcriptome analyses to identify the molecular signatures of several distinct mesenchymal progenitor cell populations present in early mouse forelimb buds...
May 10, 2019: Development
Amsha Proag, Bruno Monier, Magali Suzanne
Tissue mechanics play a crucial role in organ development. They rely on the properties of cells and the extracellular matrix (ECM), but the relative physical contribution of cells and ECM to morphogenesis is poorly understood. Here, we analyzed the behavior of the peripodial epithelium (PE) of the Drosophila leg disc in the light of the dynamics of its cellular and ECM components. The PE undergoes successive changes during leg development, including elongation, opening and removal to free the leg. During elongation, we found that the ECM and cell layer are progressively uncoupled...
May 7, 2019: Development
Stephanie Herrlinger, Qiang Shao, Mei Yang, Qing Chang, Yang Liu, Xiaohan Pan, Hang Yin, Li-Wei Xie, Jian-Fu Chen
Neural progenitor cells (NPCs) undergo rapid proliferation during neurulation. This rapid growth generates a high demand for mRNA translation in a timing-dependent manner, but its underlying mechanism remains poorly understood. Lin28 is an RNA-binding protein with two paralogs, Lin28a and Lin28b, in mammals. Mice with Lin28b deletion exhibit no developmental defects, whereas we previously reported that Lin28a deletion led to microcephaly. Here we found that Lin28a/b double knockout (dKO) mice displayed neural tube defects (NTDs) coupled with reduced proliferation and precocious differentiation of NPCs...
May 7, 2019: Development
Julia Deathridge, Vlatka Antolović, Maddy Parsons, Jonathan R Chubb
Stimulation of the ERK/MAPK pathway is required for the exit from pluripotency and onset of differentiation in mouse embryonic stem cells (ESCs). The dynamic behavior of ERK activity in individual cells during this transition is unclear. Using a FRET-based biosensor, we monitored ERK signaling dynamics of single mouse ESCs during differentiation. ERK activity was highly heterogeneous, with considerable variability in ERK signaling between single cells within ESC colonies. Different triggers of differentiation induced distinct ERK activity profiles...
May 7, 2019: Development
Debashish U Menon, Yoichiro Shibata, Weipeng Mu, Terry Magnuson
A deficiency in BRG1, the catalytic subunit of the SWI/SNF chromatin remodeling complex, results in a meiotic arrest during spermatogenesis. Here, we explore the causative mechanisms. BRG1 is preferentially enriched at active promoters of genes essential for spermatogonial pluripotency and meiosis. In contrast, BRG1 is also associated with the repression of somatic genes. Chromatin accessibility at these target promoters is dependent upon BRG1. These results favor a model where BRG1 coordinates spermatogenic transcription to ensure meiotic progression...
May 1, 2019: Development
Nicole Camara, Cale Whitworth, Abigail Dove, Mark Van Doren
Sex-specific development of the gonads is a key aspect of sexual dimorphism that is regulated by Doublesex/Mab3 Related Transcription Factors (DMRTs) in diverse animal species. We find that in mutants for Drosophila dsx , important components of the male and female gonad stem cell niches (hubs and terminal filaments/cap cells, respectively) still form. Initially, gonads in all dsx mutants (both XX and XY) initiate the male program of development, but later half of these gonads switch to form female stem cell niche structures...
May 1, 2019: Development
Ning Wang, Kristine S Bagdassarian, Rebecca E Doherty, Johannes T Kroon, Katherine A Connor, Xiao Y Wang, Wei Wang, Ian H Jermyn, Simon R Turner, J Peter Etchells
In plants, cells do not migrate. Tissues are frequently arranged in concentric rings, thus expansion of inner layers is coordinated with cell division and/or expansion of cells in outer layers. In Arabidopsis stems, receptor kinases, PXY and ER , genetically interact to coordinate vascular proliferation and organisation via inter-tissue signalling. The contribution of PXY and ER paralogues to stem patterning is not known, nor is their function understood in hypocotyls, which undergo considerable radial expansion...
May 1, 2019: Development
Elena Sena, Nathalie Rocques, Caroline Borday, Harem Sabr Muhamad Amin, Karine Parain, David Sitbon, Albert Chesneau, Béatrice C Durand
A hallmark of Wnt/β-Catenin signaling is the extreme diversity of its transcriptional response, which varies depending on cell and developmental context. What controls this diversity is poorly understood. In all cases, the switch from transcriptional repression to activation depends on a nuclear increase in β-Catenin, which detaches the transcription factor T-cell Factor-7 like 1 (Tcf7l1) bound to Groucho (Gro) transcriptional co-repressors from its DNA binding sites and transiently converts Tcf7/Lymphoid enhancer binding factor 1 (Lef1) into a transcriptional activator...
April 29, 2019: Development
Isabelle Schneider, Jennifer Kreis, Axel Schweickert, Martin Blum, Philipp Vick
Organ left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). While the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development are conserved, diverging results from different model organisms suggested a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development...
April 29, 2019: Development
Guillermo Martínez-Corrales, Pablo Cabrero, Julian A T Dow, Selim Terhzaz, Shireen-A Davies
The GATA family of transcription factors is implicated in numerous developmental and physiological processes in metazoans. In Drosophila melanogaster, 5 different GATA factors ( pannier, serpent, grain, GATAd and GATAe ) have been reported as essential in the development and identity of multiple tissues, including the midgut, heart and brain. Here, we present a novel role of GATAe in the function and homeostasis of the Drosophila renal (Malpighian) tubule. We demonstrate that reduced levels of GATAe gene expression in tubule principal cells induce uncontroled cell proliferation, resulting in tumorous growth with associated altered expression of apoptotic and carcinogenic key genes...
April 29, 2019: Development
Jared C Talbot, Emily M Teets, Dhanushika Ratnayake, Phan Q Duy, Peter D Currie, Sharon L Amacher
Muscle precursors need to be correctly positioned during embryonic development for proper body movement. In zebrafish, a subset of hypaxial muscle precursors from the anterior somites undergo long-range migration, moving away from the trunk in three streams to form muscles in distal locations like the fin. We mapped long-distance muscle precursor migrations with unprecedented resolution using live imaging. We identified conserved genes necessary for normal precursor motility ( six1a, six1b, six4a, six4b and met )...
April 25, 2019: Development
Ellen K Velte, Bryan A Niedenberger, Nicholas D Serra, Anukriti Singh, Lorena Roa-DeLaCruz, Brian P Hermann, Christopher B Geyer
In the mammalian testis, sustained spermatogenesis relies on spermatogonial stem cells (SSCs); their progeny remain as stem cells (self-renewal) or proliferate and differentiate to enter meiosis in response to retinoic acid (RA). Here, we sought to uncover elusive mechanisms regulating a key switch fundamental to spermatogonial fate, the capacity of spermatogonia to respond to RA. Using the developing mouse testis as a model, we found that spermatogonia and precursor prospermatogonia exhibit a heterogeneous capacity to respond to RA with at least two underlying causes...
April 25, 2019: Development
Shlomit Edri, Penny Hayward, Peter Baillie-Johnson, Benjamin Steventon, Alfonso Martinez Arias
The mammalian embryos Caudal Lateral Epiblast harbours bipotent progenitors that contribute to the spinal cord and the paraxial mesoderm in concert with the body axis elongation. These progenitors, called Neural Mesodermal Progenitors (NMPs) are identified as cells coexpressing Sox2 and T/Brachyury , a criterion used to derive NMP-like cells from embryonic stem cells in vitro However, these progenitors do not self renew, as embryonic NMPs do. Here we find that protocols that yield NMP-like cells in vitro first produce a multipotent population that, in addition to NMPs, generate progenitors for the lateral plate and intermediate mesoderm...
April 25, 2019: Development
Leshana Saint-Jean, Nikolaos Barkas, Cristina Harmelink, Kevin L Tompkins, Rebecca J Oakey, H Scott Baldwin
The endocardium interacts with the myocardium to promote proliferation and morphogenesis during the later stages of heart development. However, the role of the endocardium in early cardiac ontogeny remains under-explored. Given the shared origin, subsequent juxtaposition, and essential cell-cell interactions of endocardial and myocardial cells throughout heart development, we hypothesized that paracrine signaling from the endocardium to the myocardium is critical for initiating early differentiation of myocardial cells...
April 25, 2019: Development
M E Dowdle, S Park, S Blaser, C A Fox, D W Houston, M D Sheets
Bicaudal-C (Bicc1) is a conserved RNA binding protein that represses the translation of selected mRNAs to control development. In Xenopus embryos Bicc1 binds and represses specific maternal mRNAs to control anterior-posterior cell fates. However, it is not known how Bicc1 binds its RNA targets or how binding affects Bicc1-dependent embryogenesis. Focusing on the KH domains, we analyzed Bicc1 mutants for their ability to bind RNA substrates in vivo and in vitro Analyses of these Bicc1 mutants demonstrated that a single KH domain, KH2 was critical for RNA binding in vivo and in vitro , while the KH1 and KH3 domains contributed minimally...
April 25, 2019: Development
Heidi Connahs, Sham Tlili, Jelle van Creij, Tricia Y J Loo, Tirtha Das Banerjee, Timothy E Saunders, Antónia Monteiro
Eyespots on the wings of nymphalid butterflies represent colorful examples of pattern formation, yet the developmental origins and mechanisms underlying eyespot center differentiation are still poorly understood. Using CRISPR-Cas9 we re-examine the function of Distal-less ( Dll ) as an activator or repressor of eyespots, a topic that remains controversial. We show that the phenotypic outcome of CRISPR mutations depends upon which specific exon is targeted. In Bicyclus anynana , exon 2 mutations are associated with both missing and ectopic eyespots and also exon-skipping...
April 16, 2019: Development
Vanesa Jiménez-Amilburu, Didier Y R Stainier
Tissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential to form a functional ventricular wall. Here we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes and colocalizes with the junctional protein ZO-1...
April 16, 2019: Development
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