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Developmental Biology
Transcriptional Pre-patterning of Drosophila Gastrulation
Feb 21, 2017   Current Biology : CB
Lim B, Levine M, Yamazaki Y
Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional program
Feb 21, 2017   Development (Cambridge, England)
Stevens ML, Chaturvedi P, Rankin SA, Macdonald M, Jagannathan S, Yukawa M, Barski A, Zorn AM
Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional program
Feb 21, 2017
Development (Cambridge, England)
UNASSIGNED: Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of © 2017. Published by The Company of Biologists Ltd.
On the development of the hepatopancreatic ductal system
Feb 19, 2017   Seminars In Cell & Developmental Biology
Villasenor A, Stainier DY
On the development of the hepatopancreatic ductal system
Feb 19, 2017
Seminars In Cell & Developmental Biology
UNASSIGNED: The hepatopancreatic ductal system is the collection of ducts that connect the liver and pancreas to the digestive tract. The formation of this system is necessary for the transport of exocrine secretions, for the correct assembly of the pancreatobiliary ductal system, and for the overall function of the digestive system. Studies on endoderm organ formation have significantly advanced our understanding of the molecular mechanisms that govern organ induction, organ specification and morphogenesis of the major foregut-derived organs. However, little is known about the mechanisms that control the development of the hepatopancreatic ductal system. Here, we provide a description of the different components of the system, summarize its development from the endoderm to a complex system of tubes, list the pathologies produced by anomalies in its development, as well as the molecules and signaling pathways that are known to be involved in its formation. Finally, we discuss its proposed potential as a multipotent cell reservoir and the unresolved questions in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.
Nodal and BMP expression during the transition to pentamery in the sea urchin Heliocidaris erythrogramma: insights into patterning the enigmatic echinoderm body plan
Feb 14, 2017   BMC Developmental Biology
Koop D, Cisternas P, Morris VB, Strbenac D, Yang JY, Wray GA, Byrne M
Nodal and BMP expression during the transition to pentamery in the sea urchin Heliocidaris erythrogramma: insights into patterning the enigmatic echinoderm body plan
Feb 14, 2017
BMC Developmental Biology
BACKGROUND: The molecular mechanisms underlying the development of the unusual echinoderm pentameral body plan and their likeness to mechanisms underlying the development of the bilateral plans of other deuterostomes are of interest in tracing body plan evolution. In this first study of the spatial expression of genes associated with Nodal and BMP2/4 signalling during the transition to pentamery in sea urchins, we investigate Heliocidaris erythrogramma, a species that provides access to the developing adult rudiment within days of fertilization. RESULTS: BMP2/4, and the putative downstream genes, Six1/2, Eya, Tbx2/3 and Msx were expressed in the earliest morphological manifestation of pentamery during development, the five hydrocoele lobes. The formation of the vestibular ectoderm, the specialized region overlying the left coelom that forms adult ectoderm, involved the expression of putative Nodal target genes Chordin, Gsc and BMP2/4 and putative BMP2/4 target genes Dlx, Msx and Tbx. The expression of Nodal, Lefty and Pitx2 in the right ectoderm, and Pitx2 in the right coelom, was as previously observed in other sea urchins. CONCLUSION: That genes associated with Nodal and BMP2/4 signalling are expressed in the hydrocoele lobes, indicates that they have a role in the developmental transition to pentamery, contributing to our understanding of how the most unusual body plan in the Bilateria may have evolved. We suggest that the Nodal and BMP2/4 signalling cascades might have been duplicated or split during the evolution to pentamery.
Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential
Feb 14, 2017   Nature Communications
Bardot E, Calderon D, Santoriello F, Han S, Cheung K, Jadhav B, Burtscher I, Artap S, Jain R, Epstein J, Lickert H, Gouon-Evans V, Sharp AJ, Dubois NC
Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential
Feb 14, 2017
Nature Communications
UNASSIGNED: The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding of cardiac development. However, the mechanisms that direct atrial versus ventricular specification remain largely unknown. Here we report the identification of a progenitor population that gives rise primarily to cardiovascular cells of the ventricles and only to few atrial cells (
New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems
Feb 20, 2017   International Review Of Cell And Molecular Biology
Zieger E, Schubert M
New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems
Feb 20, 2017
International Review Of Cell And Molecular Biology
UNASSIGNED: Secreted chiefly from the underlying mesoderm, the morphogen retinoic acid (RA) is well known to contribute to the specification, patterning, and differentiation of neural progenitors in the developing vertebrate nervous system. Furthermore, RA influences the subtype identity and neurotransmitter phenotype of subsets of maturing neurons, although relatively little is known about how these functions are mediated. This review provides a comprehensive overview of the roles played by RA signaling during the formation of the central and peripheral nervous systems of vertebrates and highlights its effects on the differentiation of several neurotransmitter systems. In addition, the evolutionary history of the RA signaling system is discussed, revealing both conserved properties and alternate modes of RA action. It is proposed that comparative approaches should be employed systematically to expand our knowledge of the context-dependent cellular mechanisms controlled by the multifunctional signaling molecule RA. © 2017 Elsevier Inc. All rights reserved.
Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study
Feb 23, 2017   PLoS Neglected Tropical Diseases
Xavier-Neto J, Carvalho M, Pascoalino BD, Cardoso AC, Costa ÂM,   . . . . . .   , Freitas-Junior L, Holanda de Freitas CB, Teixeira MM, Bevilacqua E, Franchini K
Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study
Feb 23, 2017
PLoS Neglected Tropical Diseases
The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5-9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes.
The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation
Feb 20, 2017   Developmental Cell
Morita H, Grigolon S, Bock M, Krens SF, Salbreux G, Heisenberg CP
The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation
Feb 20, 2017
Developmental Cell
UNASSIGNED: Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during "doming," when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction. Copyright © 2017 Elsevier Inc. All rights reserved.
Mutations in Genes Encoding Polycomb Repressive Complex 2 Subunits Cause Weaver Syndrome
Feb 23, 2017   Human Mutation
Imagawa E, Higashimoto K, Sakai Y, Numakura C, Okamoto N,   . . . . . .   , Miyatake S, Nakashima M, Miyake N, Soejima H, Matsumoto N
Mutations in Genes Encoding Polycomb Repressive Complex 2 Subunits Cause Weaver Syndrome
Feb 23, 2017
Human Mutation
Weaver syndrome is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected Weaver syndrome by whole exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c.707G>C, p.Arg236Thr) in EED (individual 2), and a missense mutation (c.1829A>T, p.Glu610Val) in SUZ12 (suppressor of zeste 12 homolog) (individual 3) inherited from her father (individual 4) with a mosaic mutation. SUZ12 is another component of PRC2 and germline mutations in SUZ12 have not been previously reported in humans. In vitro functional analyses demonstrated that the identified EED and SUZ12 missense mutations cause decreased trimethylation of lysine 27 of histone H3. These data indicate that loss-of-function mutations of PRC2 components are an important cause of Weaver syndrome. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Flotillins control zebrafish epiboly through their role in cadherin-mediated cell-cell adhesion
Feb 22, 2017   Biology Of The Cell
Morris EA, Bodin S, Delaval B, Comunale F, Georget V, Costa ML, Lutfalla G, Gauthier-Rouvière C
Flotillins control zebrafish epiboly through their role in cadherin-mediated cell-cell adhesion
Feb 22, 2017
Biology Of The Cell
UNASSIGNED: Zebrafish gastrulation and particularly epiboly that involves coordinated movements of several cell layers is a dynamic process for which regulators remain to be identified. We show here that Flotillin 1 and 2, ubiquitous and highly conserved proteins, are required for epiboly. Flotillins knockdown compromised embryo survival, strongly delayed epiboly and impaired deep cell radial intercalation and directed collective migration without affecting enveloping layer cell movement. At the molecular level, we identified that Flotillins are required for the formation of E-cadherin-mediated cell-cell junctions. These results provide the first in vivo evidence that Flotillins regulate E-cadherin-mediated cell-cell junctions to allow epiboly progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Stat3/Cdc25a-dependent cell proliferation promotes embryonic axis extension during zebrafish gastrulation
Feb 21, 2017   PLoS Genetics
Liu Y, Sepich DS, Solnica-Krezel L
Stat3/Cdc25a-dependent cell proliferation promotes embryonic axis extension during zebrafish gastrulation
Feb 21, 2017
PLoS Genetics
UNASSIGNED: Cell proliferation has generally been considered dispensable for anteroposterior extension of embryonic axis during vertebrate gastrulation. Signal transducer and activator of transcription 3 (Stat3), a conserved controller of cell proliferation, survival and regeneration, is associated with human scoliosis, cancer and Hyper IgE Syndrome. Zebrafish Stat3 was proposed to govern convergence and extension gastrulation movements in part by promoting Wnt/Planar Cell Polarity (PCP) signaling, a conserved regulator of mediolaterally polarized cell behaviors. Here, using zebrafish stat3 null mutants and pharmacological tools, we demonstrate that cell proliferation contributes to anteroposterior embryonic axis extension. Zebrafish embryos lacking maternal and zygotic Stat3 expression exhibit normal convergence movements and planar cell polarity signaling, but transient axis elongation defect due to insufficient number of cells resulting largely from reduced cell proliferation and increased apoptosis. Pharmacologic inhibition of cell proliferation during gastrulation phenocopied axis elongation defects. Stat3 regulates cell proliferation and axis extension in part via upregulation of Cdc25a expression during oogenesis. Accordingly, restoring Cdc25a expression in stat3 mutants partially suppressed cell proliferation and gastrulation defects. During later development, stat3 mutant zebrafish exhibit stunted growth, scoliosis, excessive inflammation, and fail to thrive, affording a genetic tool to study Stat3 function in vertebrate development, regeneration, and disease.
Rbm46 regulates mouse embryonic stem cell differentiation by targeting β-Catenin mRNA for degradation
Feb 17, 2017   PloS One
Zhai L, Wang C, Chen Y, Zhou S, Li L
Rbm46 regulates mouse embryonic stem cell differentiation by targeting β-Catenin mRNA for degradation
Feb 17, 2017
PloS One
UNASSIGNED: Embryonic stem cells (ESCs) are pluripotent cells and have the capability for differentiation into any of the three embryonic germ layers. The Wnt/β-Catenin pathway has been shown to play an essential role in ESC differentiation regulation. Activation of β-Catenin by post-translational modification has been extensively studied. However, mechanism(s) of post-transcriptional regulation of β-Catenin are not well defined. In this study, we report an RNA recognition motif-containing protein (RNA binding motif protein 46, RBM46) which regulates the degradation of β-Catenin mRNA. Our results show that Rbm46 is distributed primarily in the cytoplasm of mouse ESCs (mESCs) and is elevated during the process of ESC differentiation. In addition, overexpression of Rbm46 results in differentiation of mESCs into trophectoderm, while knock-down of Rbm46 leads to mESC differentiation into endoderm. β-Catenin, a key effector in the Wnt pathway which has been reported to play a significant role in the regulation of ESC differentiation, is post-transcriptionally regulated by Rbm46. Our study reveals Rbm46 plays a novel role in the regulation of ESC differentiation.
Ubiquitin C-terminal hydrolase37 regulates Tcf7 DNA binding for the activation of Wnt signalling
Feb 15, 2017   Scientific Reports
Han W, Lee H, Han JK
Ubiquitin C-terminal hydrolase37 regulates Tcf7 DNA binding for the activation of Wnt signalling
Feb 15, 2017
Scientific Reports
UNASSIGNED: The Tcf/Lef family of transcription factors mediates the Wnt/β-catenin pathway that is involved in a wide range of biological processes, including vertebrate embryogenesis and diverse pathogenesis. Post-translational modifications, including phosphorylation, sumoylation and acetylation, are known to be important for the regulation of Tcf/Lef proteins. However, the importance of ubiquitination and ubiquitin-mediated regulatory mechanisms for Tcf/Lef activity are still unclear. Here, we newly show that ubiquitin C-terminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt signalling. Biochemical analyses demonstrated that deubiquitinating activity of Uch37 is not involved in Tcf7 protein stability but is required for the association of Tcf7 to target gene promoter in both Xenopus embryo and human liver cancer cells. In vivo analyses further revealed that Uch37 functions as a positive regulator of the Wnt/β-catenin pathway downstream of β-catenin stabilization that is required for the expression of ventrolateral mesoderm genes during Xenopus gastrulation. Our study provides a new mechanism for chromatin occupancy of Tcf7 and uncovers the physiological significance of Uch37 during early vertebrate development by regulating the Wnt/β-catenin pathway.
Type II congenital pulmonary airway malformation associated with intralobar pulmonary sequestration: report of a case and review of classification criteria
Feb 14, 2017   Pathologica
Mastrogiulio MG, Barone A, Disanto MG, Ginori A, Ambrosio MR, Carbone SF, Spina D
Type II congenital pulmonary airway malformation associated with intralobar pulmonary sequestration: report of a case and review of classification criteria
Feb 14, 2017
Pathologica
UNASSIGNED: Pulmonary congenital abnormalities are rare disorders including congenital pulmonary airway malformations (CPAM) and pulmonary sequestration (PS). CPAM is a lesion characterized by the presence of anomalous bronchiolar or acinar structures, variable in size, either cystic or not cystic. PS is generally defined as nonfunctioning lung tissue that is not in normal continuity with the tracheobronchial tree and that derives its blood supply from systemic vessels. We describe a case of a baby girl with a very rare association between CPAM type 2 and intralobar pulmonary sequestration (IPS) focusing on the cystic lesions typical of CPAM and on the lymphatic and blood vessels. The cells lining the cysts often were positive for D2-40 (oncofetal protein M2A). Lymphatic endothelial cells, positive for D2-40, were widely present in the lung parenchyma and dilated lymphatic vessels were present also in the inter-alveolar septa. Moreover, we discuss the pathogenesis of CPAM and its classification criteria. © Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.
Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
Feb 13, 2017   PloS One
Raza QS, Vanderploeg JL, Jacobs JR
Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
Feb 13, 2017
PloS One
Matrix Metalloproteinases (Mmps) degrade glycoproteins and proteoglycans of the extracellular matrix (ECM) or cell surface and are crucial for morphogenesis. Mmps and their inhibitors are expressed during early stages of cardiac development in vertebrates and expression is altered in multiple congenital cardiomyopathies such as cardia bifida. Drosophila genome encodes two copies of Mmps, Mmp1 and Mmp2 whereas in humans up to 25 Mmps have been identified with overlapping functions. We investigated the role of Mmps during embryonic heart development in Drosophila, a process which is morphogenetically similar to early heart tube formation in vertebrates. We demonstrate that the two Mmps in Drosophila have distinct and overlapping roles in cell motility, cell adhesion and cardiac lumenogenesis. We determined that Mmp1 and Mmp2 promote Leading Edge membrane dynamics of cardioblasts during collective migration. Mmp2 is essential for cardiac lumen formation, and mutants generate a cardia bifida phenotype. Mmp1 is required for luminal expansion. Mmp1 and Mmp2 both localise to the basal domains of cardiac cells, however, occupy non-overlapping domains apically. Mmp1 and Mmp2 regulate the proteoglycan composition and size of the apical and basal ECM, yet only Mmp2 is required to restrict ECM assembly to the lumen. Mmp1 negatively regulates the size of the adhesive Cadherin cell surface domain, whereas in a complementary fashion, Mmp2 negatively regulates the size of the Integrin-ECM domain and thereby prescribes the domain to establish and restrict Slit morphogen signalling. Inhibition of Mmp activity through ectopic expression of Tissue Inhibitor of Metalloproteinase in the ectoderm blocks lumen formation. Therefore, Mmp expression and function identifies ECM differentiation and remodelling as a key element for cell polarisation and organogenesis.
Evo-engineering and the cellular and molecular origins of the vertebrate spinal cord
Feb 13, 2017   Developmental Biology
Steventon B, Martinez Arias A
Evo-engineering and the cellular and molecular origins of the vertebrate spinal cord
Feb 13, 2017
Developmental Biology
UNASSIGNED: The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate them to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development. Copyright © 2017. Published by Elsevier Inc.
From egg to "no-body": an overview and revision of developmental pathways in the ancient arthropod lineage Pycnogonida
Feb 13, 2017   Frontiers In Zoology
Brenneis G, Bogomolova EV, Arango CP, Krapp F
From egg to "no-body": an overview and revision of developmental pathways in the ancient arthropod lineage Pycnogonida
Feb 13, 2017
Frontiers In Zoology
BACKGROUND: Arthropod diversity is unparalleled in the animal kingdom. The study of ontogeny is pivotal to understand which developmental processes underlie the incredible morphological disparity of arthropods and thus to eventually unravel evolutionary transformations leading to their success. Work on laboratory model organisms has yielded in-depth data on numerous developmental mechanisms in arthropods. Yet, although the range of studied taxa has increased noticeably since the advent of comparative evolutionary developmental biology (evo-devo), several smaller groups remain understudied. This includes the bizarre Pycnogonida (sea spiders) or "no-bodies", a taxon occupying a crucial phylogenetic position for the interpretation of arthropod development and evolution. RESULTS: Pycnogonid development is variable at familial and generic levels and sometimes even congeneric species exhibit different developmental modes. Here, we summarize the available data since the late 19 CONCLUSIONS: A resurgence of studies on pycnogonid postembryonic development has provided various new insights in the last decades. However, the scarcity of modern-day embryonic data - including the virtual lack of gene expression and functional studies - needs to be addressed in future investigations to strengthen comparisons to other arthropods and arthropod outgroups in the framework of evo-devo. Our review may serve as a basis for an informed choice of target species for such studies, which will not only shed light on chelicerate development and evolution but furthermore hold the potential to contribute important insights into the anamorphic development of the arthropod ancestor.
Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development
Feb 15, 2017   Cell Stem Cell
Shi ZD, Lee K, Yang D, Amin S, Verma N, Li QV, Zhu Z, Soh CL, Kumar R, Evans T, Chen S, Huangfu D
Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development
Feb 15, 2017
Cell Stem Cell
UNASSIGNED: Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6.1+ stage, leading to impaired formation of glucose-responsive β-like cells. In addition to this GATA6 haploinsufficiency, we also identified dosage-sensitive requirements for GATA6 and GATA4 in the formation of both definitive endoderm and pancreatic progenitor cells. Our work expands the application of hPSCs from studying the impact of individual gene loci to investigation of multigenic human traits, and it establishes an approach for identifying genetic modifiers of human disease. Copyright © 2017 Elsevier Inc. All rights reserved.
GATA6 Plays an Important Role in the Induction of Human Definitive Endoderm, Development of the Pancreas, and Functionality of Pancreatic β Cells
Feb 15, 2017   Stem Cell Reports
Tiyaboonchai A, Cardenas-Diaz FL, Ying L, Maguire JA, Sim X, Jobaliya C, Gagne AL, Kishore S, Stanescu DE, Hughes N, De Leon DD, French DL, Gadue P
GATA6 Plays an Important Role in the Induction of Human Definitive Endoderm, Development of the Pancreas, and Functionality of Pancreatic β Cells
Feb 15, 2017
Stem Cell Reports
UNASSIGNED: Induced pluripotent stem cells were created from a pancreas agenesis patient with a mutation in GATA6. Using genome-editing technology, additional stem cell lines with mutations in both GATA6 alleles were generated and demonstrated a severe block in definitive endoderm induction, which could be rescued by re-expression of several different GATA family members. Using the endodermal progenitor stem cell culture system to bypass the developmental block at the endoderm stage, cell lines with mutations in one or both GATA6 alleles could be differentiated into β-like cells but with reduced efficiency. Use of suboptimal doses of retinoic acid during pancreas specification revealed a more severe phenotype, more closely mimicking the patient's disease. GATA6 mutant β-like cells fail to secrete insulin upon glucose stimulation and demonstrate defective insulin processing. These data show that GATA6 plays a critical role in endoderm and pancreas specification and β-like cell functionality in humans. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
The Origin of Vertebrate Gills
Feb 13, 2017   Current Biology : CB
Gillis JA, Tidswell OR
The Origin of Vertebrate Gills
Feb 13, 2017
Current Biology : CB
UNASSIGNED: Pharyngeal gills are a fundamental feature of the vertebrate body plan [1]. However, the evolutionary history of vertebrate gills has been the subject of a long-standing controversy [2-8]. It is thought that gills evolved independently in cyclostomes (jawless vertebrates-lampreys and hagfish) and gnathostomes (jawed vertebrates-cartilaginous and bony fishes), based on their distinct embryonic origins: the gills of cyclostomes derive from endoderm [9-12], while gnathostome gills were classically thought to derive from ectoderm [10, 13]. Here, we demonstrate by cell lineage tracing that the gills of a cartilaginous fish, the little skate (Leucoraja erinacea), are in fact endodermally derived. This finding supports the homology of gills in cyclostomes and gnathostomes, and a single origin of pharyngeal gills prior to the divergence of these two ancient vertebrate lineages. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Colonic mesenchyme differentiates into smooth muscle before its colonization by vagal enteric neural crest-derived cells in the chick embryo
Feb 15, 2017   Cell And Tissue Research
Bourret A, Chauvet N, de Santa Barbara P, Faure S
Colonic mesenchyme differentiates into smooth muscle before its colonization by vagal enteric neural crest-derived cells in the chick embryo
Feb 15, 2017
Cell And Tissue Research
UNASSIGNED: During development, the gastrointestinal (GI) tract arises from a primary tube composed of mesoderm and endoderm. The mesoderm gives rise to the digestive mesenchyme, which in turn differentiates into multiple tissues, namely the submucosa, the interstitial cells of Cajal and the smooth muscle cells (SMCs). Concomitant with these early patterning events, the primitive GI tract is colonized by vagal enteric neural crest-derived cells (vENCDCs), a population of cells that gives rise to the enteric nervous system, the intrinsic innervation of the GI tract. Reciprocal neuro-mesenchymal interactions are essential for the coordinated development of GI musculature. The aim of this study is to examine and compare the kinetics of mesenchymal cell differentiation into SMCs along the anterior-posterior axis to the pattern of vENCDCs migration using whole-mount in situ hybridization and paraffin section immunofluorescence analyses on chick embryonic GI tracts from E4-Stage 23 to E7-Stages 30-31. We confirmed that gastric and pre-umbilical intestine mesenchyme differentiation into SMCs occurs after vENCDCs colonization. However, we found that colonic and post-umbilical intestine mesenchyme differentiation occurs before vENCDCs colonization. These findings suggest that regional-specific mechanisms are involved in the mesenchyme differentiation into SMCs along the GI anterior-posterior axis.
Angled Growth of the Dental Lamina Is Accompanied by Asymmetrical Expression of the WNT Pathway Receptor Frizzled 6
Feb 15, 2017   Frontiers In Physiology
Putnová I, Dosedělová H, Bryja V, Landová M, Buchtová M, Štembírek J
Angled Growth of the Dental Lamina Is Accompanied by Asymmetrical Expression of the WNT Pathway Receptor Frizzled 6
Feb 15, 2017
Frontiers In Physiology
UNASSIGNED: Frizzled 6 (FZD6) belongs to a family of proteins that serve as receptors in the WNT signaling pathway. FZD6 plays an important role in the establishment of planar cell polarity in many embryonic processes such as convergent extension during gastrulation, neural tube closure, or hair patterning. Based on its role during hair development, we hypothesized that FZD6 may have similar expression pattern and function in the dental lamina, which is also a distinct epithelial protrusion growing characteristically angled into the mesenchyme. Diphyodont minipig was selected as a model species because its dentition closely resemble human ones with successional generation of teeth initiated from the dental lamina. We revealed asymmetrical expression of FZD6 in the dental lamina of early as well as late stages during its regression with stronger expression located on the labial side of the dental lamina. During lamina regression, FZD6-positive cells were found in its superficial part and the signal coincided with the upregulation of molecules involved in epithelial-mesenchymal transition and increased migratory potential of epithelial cells. FZD6-expression was also turned on during differentiation of cells producing hard tissues, in which mature odontoblasts, ameloblasts, or surrounding osteoblasts were FZD6-positive. On the other hand, the tip of successional lamina and its lingual part, in which progenitor cells are located, exhibited FZD6-negativity. In conclusion, asymmetrical expression of FZD6 correlates with the growth directionality and side-specific morphological differences in the dental lamina of diphyodont species. Based on observed expression pattern, we propose that the dental lamina is other epithelial tissue, where planar cell polarity signaling is involved during its asymmetrical growth.
Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm
Feb 16, 2017   BMC Biotechnology
Koga T, Shiraki N, Yano S, Suico MA, Morino-Koga S, Sato T, Shuto T, Kume S, Kai H
Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm
Feb 16, 2017
BMC Biotechnology
BACKGROUND: Because of the increasing number of diabetic patients, it is important to generate pancreatic and duodenal homeobox gene 1 (Pdx1)-expressing cells, which are capable of differentiating into pancreatic endocrine β cells. Mild electrical stimulation was reported to modulate the differentiation of ES cells into ectoderm-derived neuronal cells or mesoderm-derived cardiac cells. RESULTS: In this study, we report that mild electrical stimulation with heat shock (MET) potentiates the differentiation of ES cells into definitive endoderm-derived Pdx1-expressing cells. MET has no effect when applied to early definitive endoderm on differentiation day 5. A 1.87-fold increase in the proportion of Pdx1-expressing cells was observed when stimulation was applied to the late definitive endoderm one day prior to the immergence of Pdx1/GFP-expressing cells on differentiation day 7. Pdx1 mRNA was also up-regulated by MET. The potentiating effect of MET synergized with activin and basic fibroblast growth factor into Pdx1-expressing cells. Moreover, MET stimulation on late definitive endoderm up-regulated heat shock protein 72 and activated various kinases including Akt, extracellular signal-regulated kinase, p38, and c-jun NH CONCLUSIONS: Our findings indicate that MET induces the differentiation of Pdx1-expressing cells within the definitive endoderm in a time-dependent manner, and suggest useful application for regenerative medicine.

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