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https://www.readbyqxmd.com/read/28100467/an-essential-role-of-cbl-and-cbl-b-ubiquitin-ligases-in-mammary-stem-cell-maintenance
#1
Bhopal Mohapatra, Neha Zutshi, Wei An, Benjamin Goetz, Priyanka Arya, Timothy A Bielecki, Insha Mustaq, Matthew D Storck, Jane L Meza, Vimla Band, Hamid Band
CBL and CBL-B ubiquitin ligases are negative regulators of tyrosine kinase signaling with established roles in the immune system. However, their physiological roles in epithelial tissues are unknown. Here we used the MMTV-Cre-mediated Cbl gene deletion on a Cbl-b-null background as well as a tamoxifen-inducible mammary stem cell (MaSC)-specific Cbl/Cbl-b double knockout (DKO), using Lgr5-GFP-CreERT, to demonstrate a mammary epithelial cell-autonomous requirement of CBL and CBL-B in the maintenance of MaSCs...
January 18, 2017: Development
https://www.readbyqxmd.com/read/28096221/efficient-crispr-cas9-assisted-gene-targeting-enables-rapid-and-precise-genetic-manipulation-of-mammalian-neural-stem-cells
#2
Raul Bardini Bressan, Pooran Singh Dewari, Maria Kalantzaki, Ester Gangoso, Mantas Matjusaitis, Claudia Garcia-Diaz, Carla Blin, Vivien Grant, Harry Bulstrode, Sabine Gogolok, William C Skarnes, Steven M Pollard
Mammalian neural stem (NS) cell lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NS cells are clonally expandable, genetically stable, and easily transfectable - experimental attributes compatible with targeted genetic manipulations. However, gene targeting - so critical for functional studies of embryonic stem cells - has not been exploited to date in NS cells...
January 17, 2017: Development
https://www.readbyqxmd.com/read/28087639/vegfd-modulates-both-angiogenesis-and-lymphangiogenesis-during-zebrafish-embryonic-development
#3
Neil I Bower, Adam J Vogrin, Ludovic Le Guen, Huijun Chen, Steven A Stacker, Marc G Achen, Benjamin M Hogan
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, the formation of veins and lymphatics. VEGFD has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087638/intrinsic-properties-of-limb-bud-cells-can-be-differentially-reset
#4
Patricia Saiz-Lopez, Kavitha Chinnaiya, Matthew Towers, Maria A Ros
An intrinsic timing mechanism specifies the positional values of the zeugopod (i.e. radius/ulna) and then autopod (i.e. wrist/digits) segments during limb development. Here we have addressed if this timing mechanism ensures that patterning events occur only once by grafting GFP-expressing autopod progenitor cells to the earlier host signaling environment of zeugopod progenitor cells. We show that early and late autopod progenitors fated for the wrist and phalanges, respectively, both contribute to the entire host autopod indicating that the autopod positional value is irreversibly determined as revealed by Hoxa13 expression...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087637/retinoic-acid-receptor-regulation-of-epimorphic-and-homeostatic-regeneration-in-the-axolotl
#5
Matthew Nguyen, Pankhuri Singhal, Judith Piet, Sandra J Shefelbine, Malcolm Maden, S Randal Voss, James R Monaghan
Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we target specific retinoic acid receptors (RARs) to either PD duplicate (RA treatment or RARγ agonist) or truncate (RARβ antagonist) regenerating limbs...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087636/r-spondin-1-is-required-for-specification-of-hematopoietic-stem-cells-through-wnt16-and-vegfa-signaling-pathways
#6
Jamie R Genthe, Wilson K Clements
Hematopoietic stem cells (HSCs) are the therapeutic component of bone marrow transplants, but finding immune-compatible donors limits treatment availability and efficacy. Recapitulation of endogenous specification during development is a promising approach to directing HSC specification in vitro, but current protocols are not capable of generating authentic HSCs with high efficiency. Across phyla, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta concurrent with arteriovenous specification and intersegmental vessel (ISV) sprouting, processes regulated by Notch and Wnt...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#7
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087634/genome-wide-identification-of-regulatory-elements-in-sertoli-cells
#8
Danielle M Maatouk, Anirudh Natarajan, Yoichiro Shibata, Lingyun Song, Gregory E Crawford, Uwe Ohler, Blanche Capel
A current goal of molecular biology is to identify transcriptional networks regulating cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and cell types are mixed. To identify regulatory sites during sex determination, we subjected Sertoli cells from mouse fetal testes to DNaseI-seq and ChIP-seq for H3K27ac. DNaseI-seq identified putative regulatory sites around Sertoli- and pregranulosa-enriched genes; however, active enhancers marked by H3K27ac were enriched proximal only to Sertoli-enriched genes...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087633/the-abl-pathway-bifurcates-to-balance-enabled-and-rac-signaling-in-axon-patterning-in-drosophila
#9
Ramakrishnan Kannan, Jeong-Kuen Song, Tatiana Karpova, Akanni Clarke, Madhuri Shivalkar, Benjamin Wang, Lyudmila Kotlyanskaya, Irina Kuzina, Qun Gu, Edward Giniger
The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. While individual components are known, the relationships among them remain mysterious. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087632/sequential-organogenesis-sets-two-parallel-sensory-lines-in-medaka
#10
Ali Seleit, Isabel Krämer, Elizabeth Ambrosio, Nicolas Dross, Ulrike Engel, Lázaro Centanin
Animal organs are typically formed during embryogenesis by following one specific developmental programme. Here we report that neuromast organs are generated by two distinct and sequential programmes that result in parallel sensory lines in medaka embryos. A ventral posterior lateral line (pLL) is composed of neuromasts deposited by collectively migrating cells while a midline pLL is formed by individually migrating cells. Despite the variable number of neuromasts among embryos, the sequential programmes that we describe here fix an invariable ratio between ventral and midline neuromasts...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087631/papc-couples-the-segmentation-clock-to-somite-morphogenesis-by-regulating-n-cadherin-dependent-adhesion
#11
Jérome Chal, Charlène Guillot, Olivier Pourquié
Vertebrate segmentation is characterized by the periodic formation of epithelial somites from the mesenchymal presomitic mesoderm (PSM). How the rhythmic signaling pulse delivered by the Segmentation Clock is translated into the periodic morphogenesis of somites remains poorly understood. Here, we focused on the role of Paraxial protocadherin (PAPC/Pcdh8) in this process. We showed that in chicken and mouse embryos, PAPC expression is tightly regulated by the Clock and Wavefront system in the posterior PSM...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087630/reconstitution-of-torso-signaling-in-cultured-cells-suggests-a-role-for-both-trunk-and-torsolike-in-receptor-activation
#12
Smita Amarnath, Leslie M Stevens, David S Stein
Formation of the Drosophila embryonic termini is controlled by the localized activation of the receptor tyrosine kinase, Torso. Both Torso and Torso's presumed ligand, Trunk, are expressed uniformly in the early embryo. Polar activation of Torso requires Torsolike, which is expressed by follicle cells adjacent to the ends of the developing oocyte. We find that Torso expressed at high levels in cultured Drosophila cells is activated by individual application of Trunk, Torsolike or another known Torso ligand, Prothoracicotropic Hormone...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087629/jmjd2c-kdm4c-facilitates-the-assembly-of-essential-enhancer-protein-complexes-at-the-onset-of-embryonic-stem-cell-differentiation
#13
Rute A Tomaz, Jennifer L Harman, Donja Karimlou, Lauren Weavers, Lauriane Fritsch, Tony Bou-Kheir, Emma Bell, Ignacio Del Valle Torres, Kathy K Niakan, Cynthia Fisher, Onkar Joshi, Hendrik G Stunnenberg, Edward Curry, Slimane Ait-Si-Ali, Helle F Jørgensen, Véronique Azuara
Jmjd2/Kdm4 H3K9-demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we uncover that Jmjd2c facilitates this process by stabilizing the assembly of Mediator-Cohesin complexes at lineage-specific enhancers. Functionally, we show that Jmjd2c is required in ESCs to initiate appropriate gene expression programs upon somatic multi-lineage differentiation. In the absence of Jmjd2c, differentiation is stalled at an early post-implantation epiblast-like stage, while Jmjd2c-knockout ESCs remain capable of forming extra-embryonic endoderm derivatives...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087628/id4-levels-dictate-the-stem-cell-state-in-mouse-spermatogonia
#14
Aileen R Helsel, Qi-En Yang, Melissa J Oatley, Tessa Lord, Fred Sablitzky, Jon M Oatley
Spermatogenesis is a classic model of cycling cell lineages that depend on a balance between stem cell self-renewal for continuity and formation of progenitors as the initial step in production of differentiated cells. However, the mechanisms guiding the continuum of spermatogonial stem cell (SSC) to progenitor spermatogonial transition and precise identifiers of subtypes in the process are undefined. Here we used an Id4-eGfp reporter mouse to discover that EGFP intensity is predictive of the subsets with the ID4-EGFP(Bright) population being mostly, if not purely, SSCs while the ID4-EGFP(Dim) population is in transition to the progenitor state...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087627/inhibition-of-cell-polarity-establishment-in-stomatal-asymmetric-cell-division-using-the-chemical-compound-bubblin
#15
Yumiko Sakai, Shigeo S Sugano, Takashi Kawase, Makoto Shirakawa, Yu Imai, Yusuke Kawamoto, Hiroshi Sugiyama, Tsuyoshi Nakagawa, Ikuko Hara-Nishimura, Tomoo Shimada
Stem-cell polarization is a crucial step in asymmetric cell division, which is a universal system for generating cellular diversity in multicellular organisms. Several conventional genetics studies have attempted to elucidate the mechanisms underlying cell polarization in plants, but it remains largely unknown. In plants, stomata, which are valves for gas exchange, are generated through several rounds of asymmetric divisions. In this study, we identified and characterized a chemical compound that affects stomatal stem-cell polarity...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087626/snail2-and-zeb2-repress-p-cadherin-to-define-embryonic-territories-in-the-chick-embryo
#16
Hervé Acloque, Oscar H Ocaña, Diana Abad, Claudio D Stern, M Angela Nieto
Snail and Zeb transcription factors induce epithelial to mesenchymal transition (EMT) in embryonic and adult tissues by direct repression of E-Cadherin transcription. The repression of E-Cadherin transcription by the EMT inducers Snail1 and Zeb2 plays a fundamental role in defining embryonic territories in the mouse, as E-Cadherin needs to be downregulated in the primitive streak and in the epiblast concomitant with the formation of mesendodermal precursors and the neural plate, respectively. Here we show that in the chick embryo, E-Cadherin is weakly expressed in the epiblast at pre-primitive streak stages where it is substituted by P-Cadherin We also show that Snail2 and Zeb2 repress P-Cadherin transcription in the primitive streak and the neural plate, respectively...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087625/faithful-mrna-splicing-depends-on-the-prp19-complex-subunit-faint-sausage-and-is-required-for-tracheal-branching-morphogenesis-in-drosophila
#17
Julia Sauerwald, Charlotte Soneson, Mark D Robinson, Stefan Luschnig
Morphogenesis requires the dynamic regulation of gene expression, including transcription, mRNA maturation and translation. Dysfunction of the general mRNA splicing machinery can cause surprisingly specific cellular phenotypes, but the basis for these effects is not clear. Here we show that the Drosophila faint sausage (fas) locus, implicated in epithelial morphogenesis and previously reported to encode a secreted immunoglobulin domain protein, in fact encodes a subunit of the spliceosome-activating Prp19 complex, which is essential for efficient pre-mRNA splicing...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087624/tissue-specific-regulation-of-alternative-polyadenylation-represses-expression-of-neuronal-ankyrin-isoform-in-c-elegans-epidermal-development
#18
Fei Chen, Andrew D Chisholm, Yishi Jin
Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. In C. elegans, several ankyrin isoforms are produced from the unc-44 locus through alternative polyadenylation. Here, we identify a key role for an intronic polyadenylation site (PAS) in temporal- and tissue-specific regulation of UNC-44/ankyrin isoforms. Removing an intronic PAS results in ectopic expression of the neuronal ankyrin isoform in non-neural tissues. This mis-expression underlies epidermal developmental defects in mutants of the conserved tumor suppressor death-associated protein kinase, dapk-1 We previously reported that the use of this intronic PAS depends on the nuclear polyadenylation factor SYDN-1, which inhibits the RNA polymerase II CTD phosphatase SSUP-72...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087623/a-p53-based-genetic-tracing-system-to-follow-postnatal-cardiomyocyte-expansion-in-heart-regeneration
#19
Qi Xiao, Guoxin Zhang, Huijuan Wang, Lai Chen, Shuangshuang Lu, Dejing Pan, Geng Liu, Zhongzhou Yang
For heart regeneration, the proliferative potential of cardiomyocytes in postnatal mice is under intense investigations. However, solely relying on immunostaining of proliferation markers, the long term proliferation dynamics and potential of the cardiomyocytes cannot be readily addressed. Previously, we found that a p53 promoter driving reporter predominantly marked the proliferating lineages in mice. Here, we established a p53 based genetic tracing system to investigate postnatal cardiomyocyte proliferation and heart regeneration...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28049660/an-exclusive-cellular-and-molecular-network-governs-intestinal-smooth-muscle-cell-differentiation-in-vertebrates
#20
Dafne Gays, Christopher Hess, Annalisa Camporeale, Ugo Ala, Paolo Provero, Christian Mosimann, Massimo M Santoro
Intestinal smooth muscle cells (iSMCs) are a critical component of the adult gastrointestinal (GI) tract and support intestinal differentiation, peristalsis, and epithelial homeostasis during development. Despite these critical roles, the origin of iSMCs and the mechanisms responsible for their differentiation and function remain fairly unknown in vertebrates. Here, using genetic lineage tracing in zebrafish, we demonstrated that iSMCs arise from the lateral plate mesoderm (LPM) in a stepwise process. Early during organogenesis, LPM cells progressively migrate ventral to the endoderm tube wrapping the developing gut...
January 3, 2017: Development
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