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Patrick P.l. Tam - One of the best experts on this subject based on the ideXlab platform.
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Endoderm Formation: Not So Black and White Anymore
Developmental Cell, 2011Co-Authors: Patrick P.l. TamAbstract:This study illustrates how the combination of innovative genetic mouse models, embryological experimentation, and live-imaging techniques can resolve longstanding questions in Endoderm formation during early mouse development. Kwon et al. showed that cells recruited from the epiblast during germ layer formation in the mouse embryo are not always incorporated into the Endoderm in the immediate vicinity of the primitive streak. Beyond demonstrating that the mouse is just like a chick in its strategy for definitive (gut) Endoderm recruitment, this finding resolved the enigmatic observation that some epiblast-derived cells in the Endoderm are localized further from the site of ingression than anticipated based on "conventional" wisdom. Through tracking of the distribution of the visceral Endoderm pre-existing prior to gastrulation, descendants of the visceral Endoderm were found, surprisingly, to colonize the embryonic gut, thus dispelling the myth that visceral Endoderm differs from the so-called "definitive" Endoderm in its inability to contribute to the embryonic gut and that it is replaced wholesale by the nascent population recruited during gastrulation. This paper thus delineated a paradigm of mouse Endoderm formation and presented us with the challenge of determining the ultimate fates of these visceral Endoderm cells in the fetal and adult gut. This PaperPick refers to "The Endoderm of the Mouse Embryo Arises by Dynamic Widespread Intercalation of Embryonic and Extraembryonic Lineages," by G.S. Kwon, M. Viotti, and A.K. Hadjantonakis, published in October 2008. Video Abstract Dr. Hadjantonakis discusses the work of her group on using live-imaging approaches coupled with genetic labeling in the mouse embryo to uncover the behavior and contribution of the visceral Endoderm in morphogenesis of the gut Endoderm.
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O15. Rhou function and the differentiation of Endoderm progenitors
Differentiation, 2010Co-Authors: Patrick P.l. Tam, David A.f. LoebelAbstract:Fate mapping studies of the mouse embryo reveal that progenitors of the definitive or gut Endoderm are recruited from the epiblast during gastrulation and they are incorporated into a pre-existing population of visceral Endoderm which may also contribute to the tissues of the embryonic gut. The definitive Endoderm in the anterior region of the post-gastrula stage embryo is fated for forming the epithelial lining of the foregut and the tissues of the associated organs, such as the respiratory tract, thyroid, thymus, liver and pancreas. To gain insights into the molecular determinants of foregut development, we performed microarray analyses to identify Endoderm-enriched transcripts in the foregut of early-somite-stage mouse embryos. Validation by in situ hybridization reveals that the transcripts coding for an atypical Rho GTPase, Rhou, are preferentially expressed in the foregut Endoderm. Knockdown of Rhou by shRNA in embryonic stem cells affects the differentiation of Endoderm derivatives in response to Activin treatment, but not that of the mesoderm. Rhou-deficient cells in embryoid bodies also display abnormal epithelial organization. In embryos generated from the knockdown ES cells by tetraploid complementation, the cells lining the embryonic foregut lose the epithelial architecture, with reduced apical concentration of F-actin and tendency of detaching from the epithelium. Differentiation of the Rhou-deficient Endoderm is also impaired. A proper regulation of Rhou activity is therefore required for the maintenance of epithelial organization of the Endoderm which appears to be a crucial intermediate step for Endoderm differentiation.
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Regionalisation of the Endoderm progenitors and morphogenesis of the gut portals of the mouse embryo.
Mechanisms of development, 2008Co-Authors: Vanessa Franklin, Samara L. Lewis, Nicole Wong, Poh Lynn Khoo, Heidi Bildsoe, Patrick P.l. TamAbstract:This fate-mapping study reveals that the progenitors of all major parts of the embryonic gut are already present in Endoderm of the early-head-fold to early-somite stage (1-9 somites) mouse embryo. The anterior Endoderm contributes primarily to the anterior intestinal portal of the early-organogenesis stage (16-19 somites) embryo. Endoderm cells around and lateral to the node are allocated to the open "midgut" region of the embryonic gut. The posterior (post-nodal) Endoderm contributes not only to the posterior intestinal portal but also the open "midgut". Descendants of the posterior Endoderm span a length of the gut from the level of the 3rd-5th somites to the posterior end of the embryonic gut. The formation of the anterior and posterior intestinal portals is accompanied by similar repertoires of morphogenetic tissue movement. We also discovered that cells on contralateral sides of the anterior Endoderm are distributed asymmetrically to the dorsal and ventral sides of the anterior intestinal portal, heralding the acquisition of laterality by the embryonic foregut.
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sequential allocation and global pattern of movement of the definitive Endoderm in the mouse embryo during gastrulation
Development, 2007Co-Authors: Patrick P.l. Tam, Jacqueline M Gad, Samara L. Lewis, Poh Ly Khoo, Heidi Ildsoe, Nicole Wong, Tania E Tsang, Lorraine RobbAbstract:During mouse gastrulation, Endoderm cells of the dorsal foregut are recruited ahead of the ventral foregut and move to the anterior region of the embryo via different routes. Precursors of the anterior-most part of the foregut and those of the mid- and hind-gut are allocated to the Endoderm of the mid-streak-stage embryo, whereas the precursors of the rest of the foregut are recruited at later stages of gastrulation. Loss of Mixl1 function results in reduced recruitment of the definitive Endoderm, and causes cells in the Endoderm to remain stationary during gastrulation. The observation that the Endoderm cells are inherently unable to move despite the expansion of the mesoderm in the Mixl1-null mutant suggests that the movement of the Endoderm and the mesoderm is driven independently of one another.
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Definitive Endoderm of the mouse embryo: formation, cell fates, and morphogenetic function.
Developmental dynamics : an official publication of the American Association of Anatomists, 2006Co-Authors: Samara L. Lewis, Patrick P.l. TamAbstract:The Endoderm is one of the primary germ layers but, in comparison to ectoderm and mesoderm, has received less attention. The definitive Endoderm forms during gastrulation and replaces the extraembryonic visceral Endoderm. It participates in the complex morphogenesis of the gut tube and contributes to the associated visceral organs. This review highlights the role of the definitive Endoderm as a source of patterning cues for the morphogenesis of other germ-layer tissues, such as the anterior neurectoderm and the pharyngeal region, and also emphasizes the intricate patterning that the Endoderm itself undergoes enabling the acquisition of regionalized cell fates.
Janet Rossant - One of the best experts on this subject based on the ideXlab platform.
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Gut Endoderm takes flight from the wings of mesoderm
Nature Cell Biology, 2014Co-Authors: Angela C. H. Mcdonald, Janet RossantAbstract:The Endoderm layer destined to be primitive gut is a mosaic of earlier visceral Endoderm and definitive Endoderm that arises later, during gastrulation. Live imaging now reveals that in mouse embryos, definitive Endoderm cells egress from underlying mesoderm and intercalate into the overlying cell layer. This process requires SOX17-mediated control of basement membrane organization.
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BMP signaling induces visceral Endoderm differentiation of XEN cells and parietal Endoderm.
Developmental biology, 2011Co-Authors: Agnieszka Paca, Janet Rossant, Cheryle A Seguin, Melanie Clements, Michael Ryczko, Tristan A. Rodriguez, Tilo KunathAbstract:The extraembryonic Endoderm of mammals is essential for nutritive support of the fetus and patterning of the early embryo. Visceral and parietal Endoderm are major subtypes of this lineage with the former exhibiting most, if not all, of the embryonic patterning properties. Extraembryonic Endoderm (XEN) cell lines derived from the primitive Endoderm of mouse blastocysts represent a cell culture model of this lineage, but are biased towards parietal Endoderm in culture and in chimeras. In an effort to promote XEN cells to adopt visceral Endoderm character we have mimicked different aspects of the in vivo environment. We found that BMP signaling promoted a mesenchymal-to-epithelial transition of XEN cells with up-regulation of E-cadherin and down-regulation of vimentin. Gene expression analysis showed the differentiated XEN cells most resembled extraembryonic visceral Endoderm (exVE), a subtype of VE covering the extraembryonic ectoderm in the early embryo, and during gastrulation it combines with extraembryonic mesoderm to form the definitive yolk sac. We found that laminin, a major component of the extracellular matrix in the early embryo, synergised with BMP to promote highly efficient conversion of XEN cells to exVE. Inhibition of BMP signaling with the chemical inhibitor, Dorsomorphin, prevented this conversion suggesting that Smad1/5/8 activity is critical for exVE induction of XEN cells. Finally, we show that applying our new culture conditions to freshly isolated parietal Endoderm (PE) from Reichert's membrane promoted VE differentiation showing that the PE is developmentally plastic and can be reprogrammed to a VE state in response to BMP. Generation of visceral Endoderm from XEN cells uncovers the true potential of these blastocyst-derived cells and is a significant step towards modelling early developmental events ex vivo.
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establishment of Endoderm progenitors by sox transcription factor expression in human embryonic stem cells
Cell Stem Cell, 2008Co-Authors: Cheryle A Seguin, Jonathan S Draper, Andras Nagy, Janet RossantAbstract:In this study, we explore Endoderm cell fate regulation through the expression of lineage-determining transcription factors. We demonstrate that stable Endoderm progenitors can be established from human ES cells by constitutive expression of SOX7 or SOX17, producing extraembryonic Endoderm and definitive Endoderm progenitors, respectively. In teratoma assays and growth factor-mediated differentiation, SOX7 cells appear restricted to the extraembryonic Endoderm, and SOX17 cells demonstrate a mesEndodermal phenotype in teratomas and the ability to undergo Endoderm maturation in vitro in the absence of cytokine-mediated Endoderm induction. These Endoderm progenitor cells maintain a stable phenotype through many passages in culture, thereby providing new tools to explore the pathways of Endoderm differentiation.
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imprinted x inactivation in extra embryonic Endoderm cell lines from mouse blastocysts
Development, 2005Co-Authors: Tilo Kunath, R. L. Gardner, Danielle Arnaud, Ikuhiro Okamoto, Corinne Chureau, Yojiro Yamanaka, Edith Heard, Philip Avner, Janet RossantAbstract:The extra-embryonic Endoderm lineage plays a major role in the nutritive support of the embryo and is required for several inductive events, such as anterior patterning and blood island formation. Blastocyst-derived embryonic stem (ES) and trophoblast stem (TS) cell lines provide good models with which to study the development of the epiblast and trophoblast lineages, respectively. We describe the derivation and characterization of cell lines that are representative of the third lineage of the blastocyst – extra-embryonic Endoderm. Extra-embryonic Endoderm (XEN) cell lines can be reproducibly derived from mouse blastocysts and passaged without any evidence of senescence. XEN cells express markers typical of extra-embryonic Endoderm derivatives, but not those of the epiblast or trophoblast. Chimeras generated by injection of XEN cells into blastocysts showed exclusive contribution to extra-embryonic Endoderm cell types. We used female XEN cells to investigate the mechanism of X chromosome inactivation in this lineage. We observed paternally imprinted X-inactivation, consistent with observations in vivo. Based on gene expression analysis, chimera studies and imprinted X-inactivation, XEN cell lines are representative of extra-embryonic Endoderm and provide a new cell culture model of an early mammalian lineage.
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The transcription factor HNF3beta is required in visceral Endoderm for normal primitive streak morphogenesis
Development (Cambridge England), 1998Co-Authors: Daniel Dufort, Lois Schwartz, Kendraprasad Harpal, Janet RossantAbstract:During early embryogenesis, the transcription factor HNF3beta is expressed in visceral and definitive Endoderm, node, notochord and floorplate. A targeted mutation in the HNF3β gene results in the lack of a definitive node and notochord. Furthermore, lack of HNF3beta results in failure of proper primitive streak elongation. To address whether HNF3beta is required in visceral Endoderm, we have used tetraploid embryo-ES cell aggregations to generate chimeric mouse embryos with wild-type visceral Endoderm and homozygous mutant HNF3beta embryonic ectoderm or vice versa. Replacing the visceral Endoderm of mutant HNF3beta embryos rescued proper primitive streak elongation and, conversely, mutant visceral Endoderm imposed a severe embryonic-extraembryonic constriction on wild-type embryonic ectoderm. Restoration of normal streak morphogenesis was not sufficient to allow formation of the node and notochord in HNF3beta mutant embryos. Thus, our results demonstrate that HNF3beta has two separate roles in primitive streak formation. One is to act within the visceral Endoderm to promote proper streak morphogenesis. The second is autonomous to the node and its precursors and involves specification of node and notochord cell fates. HNF3beta mutant embryos rescued for the embryonic-extraembryonic constriction developed further than mutant embryos, allowing examination of later roles for HNF3beta. We show that such mutant embryos lack foregut and midgut Endoderm. In addition, left-right asymmetry is affected in the mutant embryos.
Joy Rathjen - One of the best experts on this subject based on the ideXlab platform.
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Endoderm complexity in the mouse gastrula is revealed through the expression of spink3
BioResearch Open Access, 2014Co-Authors: Hwee Ngee Goh, Peter David Rathjen, Mary Familari, Joy RathjenAbstract:Endoderm formation in the mammalian embryo occurs first in the blastocyst, when the primitive Endoderm and pluripotent cells resolve into separate lineages, and again during gastrulation, when the definitive Endoderm progenitor population emerges from the primitive streak. The formation of the definitive Endoderm can be modeled using pluripotent cell differentiation in culture. The differentiation of early primitive ectoderm-like (EPL) cells, a pluripotent cell population formed from embryonic stem (ES) cells, was used to identify and characterize definitive Endoderm formation. Expression of serine peptidase inhibitor, Kazal type 3 (Spink3) was detected in EPL cell-derived Endoderm, and in a band of Endoderm immediately distal to the embryonic-extra-embryonic boundary in pregastrula and gastrulating embryos. Later expression marked a region of Endoderm separating the yolk sac from the developing gut. In the embryo, Spink3 expression marked a region of Endoderm comprising the distal visceral Endoderm, as determined by an endocytosis assay, and the proximal region of the definitive Endoderm. This region was distinct from the more distal definitive Endoderm population, marked by thyrotropin-releasing hormone (Trh). Endoderm expressing either Spink3 or Trh could be formed during EPL cell differentiation, and the prevalence of these populations could be influenced by culture medium and growth factor addition. Moreover, further differentiation suggested that the potential of these populations differed. These approaches have revealed an unexpected complexity in the definitive Endoderm lineage, a complexity that will need to be accommodated in differentiation protocols to ensure the formation of the appropriate definitive Endoderm progenitor in the future.
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a system to enrich for primitive streak derivatives definitive Endoderm and mesoderm from pluripotent cells in culture
PLOS ONE, 2012Co-Authors: Svetlana Vassilieva, Hwee Ngee Goh, Mary Familari, Joy Rathjen, Kevin X Lau, James N Hughes, Peter D RathjenAbstract:Two lineages of Endoderm develop during mammalian embryogenesis, the primitive Endoderm in the pre-implantation blastocyst and the definitive Endoderm at gastrulation. This complexity of Endoderm cell populations is mirrored during pluripotent cell differentiation in vitro and has hindered the identification and purification of the definitive Endoderm for use as a substrate for further differentiation. The aggregation and differentiation of early primitive ectoderm-like (EPL) cells, resulting in the formation of EPL-cell derived embryoid bodies (EPLEBs), is a model of gastrulation that progresses through the sequential formation of primitive streak-like intermediates to nascent mesoderm and more differentiated mesoderm populations. EPL cell-derived EBs have been further analysed for the formation of definitive Endoderm by detailed morphological studies, gene expression and a protein uptake assay. In comparison to embryoid bodies derived from ES cells, which form primitive and definitive Endoderm, the Endoderm compartment of embryoid bodies formed from EPL cells was comprised almost exclusively of definitive Endoderm. Definitive Endoderm was defined as a population of squamous cells that expressed Sox17, CXCR4 and Trh, which formed without the prior formation of primitive Endoderm and was unable to endocytose horseradish peroxidase from the medium. Definitive Endoderm formed in EPLEBs provides a substrate for further differentiation into specific Endoderm lineages; these lineages can be used as research tools for understanding the mechanisms controlling lineage establishment and the nature of the transient intermediates formed. The similarity between mouse EPL cells and human ES cells suggests EPLEBs can be used as a model system for the development of technologies to enrich for the formation of human ES cell-derived definitive Endoderm in the future.
Didier Y R Stainier - One of the best experts on this subject based on the ideXlab platform.
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the pou domain protein spg pou2 oct4 is essential for Endoderm formation in cooperation with the hmg domain protein casanova
Developmental Cell, 2004Co-Authors: Gerlinde Reim, Takamasa Mizoguchi, Didier Y R Stainier, Yutaka Kikuchi, Michael BrandAbstract:Abstract The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm, and Endoderm. Zebrafish Endoderm differentiation starts with the activation of sox17 by casanova ( cas ). We report that spg ( pou2 / Oct4 ) is essential for Endoderm formation. Embryos devoid of maternal and zygotic spg function (MZ spg ) lack Endodermal precursors. Cell transplantations show that spg acts in early Endodermal precursors, and cas mRNA-injection into MZ spg embryos does not restore Endoderm development. spg and cas together are both necessary and sufficient to activate Endoderm development, and stimulate expression of a sox17 promoter-luciferase reporter. Endoderm and mesoderm derive from a common origin, mesEndoderm. We propose that Spg and Cas commit mesEndodermal precursors to an Endodermal fate. The joint control of Endoderm formation by spg and cas suggests that the Endodermal germlayer may be a tissue unit with distinct genetic control, thus adding genetic support to the germlayer concept in metazoan development.
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Notch signaling can regulate Endoderm formation in zebrafish.
Developmental dynamics : an official publication of the American Association of Anatomists, 2004Co-Authors: Yutaka Kikuchi, Heather Verkade, Jeremy F. Reiter, Cheol-hee Kim, Ajay B. Chitnis, Atsushi Kuroiwa, Didier Y R StainierAbstract:Early in vertebrate development, the processes of gastrulation lead to the formation of the three germ layers: ectoderm, mesoderm, and Endoderm. The mechanisms leading to the segregation of the Endoderm and mesoderm are not well understood. In mid-blastula stage zebrafish embryos, single marginal cells can give rise to both Endoderm and mesoderm (reviewed by Warga and Stainier [2002] The guts of Endoderm formation. In: Solnica-Krezel L, editor. Pattern formation in zebrafish. Berlin: Springer-Verlag. p 28-47). By the late blastula stage, however, single marginal cells generally give rise to either Endoderm or mesoderm. To investigate this segregation of the blastoderm into cells with either Endodermal or mesodermal fates, we analyzed the role of Notch signaling in this process. We show that deltaC, deltaD, and notch1 are expressed in the marginal domain of blastula stage embryos and that this expression is dependent on Nodal signaling. Activation of Notch signaling from an early stage leads to a reduction of Endodermal cells, as assessed by sox17 and foxA2 expression. We further find that this reduction in Endoderm formation by the activation of Notch signaling is preceded by a reduction in the expression of bonnie and clyde (bon) and faust/gata5, two genes necessary for Endoderm formation (Reiter et al. [1999] Genes Dev 13:2983-2995; Reiter et al. [2001] Development 128:125-135; Kikuchi et al. [2001] Genes Dev 14:1279-1289). However, activation of Notch signaling in bon mutant embryos leads to a further reduction in Endodermal cells, also arguing for a bon-independent role for Notch signaling in Endoderm formation. Altogether, these results suggest that Notch signaling plays a role in the formation of the Endoderm, possibly in its segregation from the mesoderm.
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The guts of Endoderm formation.
Results and problems in cell differentiation, 2002Co-Authors: Rachel M. Warga, Didier Y R StainierAbstract:In this chapter, we will review the formation of the definitive Endoderm, the population of cells that give rise to the lining of the digestive tract, its associated organs and the pharyngeal pouches. At the cellular level, we will describe the location and movement of Endodermal cells from the onset of epiboly until the end of gastrulation. At the molecular level, we will discuss the genes associated with Endoderm formation beginning with Nodal signaling. For convenience, we use the term involution, sometimes referred to as internalization; we also separate Endoderm formation into the pre-involution (blastula) and post-involution (gastrula) periods although of course Endoderm formation involves a continuous series of events. In addition, we refer to the cells that contribute to the Endoderm as progenitors prior to their involution and precursors after their involution.
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A molecular pathway leading to Endoderm formation in zebrafish
Current biology : CB, 1999Co-Authors: Jonathan Alexander, Didier Y R StainierAbstract:Abstract Background: Several potentially important regulators of vertebrate Endoderm development have been identified, including Activin-related growth factors and their receptors; transcriptional regulators encoded by the genes Mixer , Xsox17 , and HNF3β ; zebrafish One-eyed pinhead (Oep), a member of the Cripto/FRL-1/Cryptic family of epidermal growth factor related proteins (EGF-CFC); and the product of the zebrafish locus casanova , which plays an essential cell-autonomous role in Endoderm formation. Results: Using overexpression studies and the analysis of different zebrafish mutants, we have assembled a molecular pathway that leads to Endoderm formation. We report that a zebrafish Sox17 homologue is expressed during gastrulation exclusively in the Endoderm and that casanova mutants lack all sox17 expression. Overexpression of mixer induces ectopic sox17 -expressing cells in wild-type embryos and promotes Endoderm formation in oep mutants, but does not rescue sox17 expression or Endoderm formation in casanova mutants. Overexpression of a constitutively active form of the type I transforming growth factor β (TGF-β) receptor TARAM-A also promotes sox17 expression in wild-type and oep mutant embryos, but not in casanova mutants. We also show that the Nodal-related molecules Cyclops and Squint and the transmembrane protein Oep are essential for normal mixer expression. Conclusions: The data indicate that the following pathway leads to zebrafish Endoderm formation: Cyclops and Squint activate receptors such as TARAM-A; Oep also appears to act upstream of such receptors; signals transduced by these receptors lead to the expression of mixer , Mixer then acts through casanova to promote the expression of sox17 and differentiation of the Endoderm.
Yi Zhang - One of the best experts on this subject based on the ideXlab platform.
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The lncRNA DEANR1 Facilitates Human Endoderm Differentiation by Activating FOXA2 Expression
Cell reports, 2015Co-Authors: Wei Jiang, Yuting Liu, Rui Liu, Kun Zhang, Yi ZhangAbstract:Long non-coding RNAs (lncRNAs) regulate diverse biological processes, including cell lineage specification. Here, we report transcriptome profiling of human Endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allows us to identify hundreds of lncRNAs that exhibit differentiation-stage-specific expression patterns. As a first step in characterizing these lncRNAs, we focus on an Endoderm-specific lncRNA, definitive Endoderm-associated lncRNA1 (DEANR1), and demonstrate that it plays an important role in human Endoderm differentiation. DEANR1 contributes to Endoderm differentiation by positively regulating expression of the Endoderm factor FOXA2. Importantly, overexpression of FOXA2 is able to rescue Endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter. Thus, our study not only reveals a large set of differentiation-stage-specific lncRNAs but also characterizes a functional lncRNA that is important for Endoderm differentiation.
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histone h3k27me3 demethylases kdm6a and kdm6b modulate definitive Endoderm differentiation from human escs by regulating wnt signaling pathway
Cell Research, 2013Co-Authors: Wei Jiang, Yi Zhang, Jinzhao WangAbstract:Definitive Endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in Endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs Endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesEndoderm and definitive Endoderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive Endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway.