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Development (Cambridge, England) Jun 2019The endoderm is a progenitor tissue that, in humans, gives rise to the majority of internal organs. Over the past few decades, genetic studies have identified many of... (Review)
Review
The endoderm is a progenitor tissue that, in humans, gives rise to the majority of internal organs. Over the past few decades, genetic studies have identified many of the upstream signals specifying endoderm identity in different model systems, revealing them to be divergent from invertebrates to vertebrates. However, more recent studies of the cell behaviours driving endodermal morphogenesis have revealed a surprising number of shared features, including cells undergoing epithelial-to-mesenchymal transitions (EMTs), collective cell migration, and mesenchymal-to-epithelial transitions (METs). In this Review, we highlight how cross-organismal studies of endoderm morphogenesis provide a useful perspective that can move our understanding of this fascinating tissue forward.
Topics: Animals; Biological Evolution; Cell Differentiation; Cell Lineage; Cell Movement; Endoderm; Epithelial-Mesenchymal Transition; Humans; Morphogenesis; Signal Transduction; Vertebrates
PubMed: 31160415
DOI: 10.1242/dev.150920 -
Developmental Biology Jun 2001Endodermally derived organs of the gastrointestinal and respiratory system form at distinct anterioposterior and dorsoventral locations along the vertebrate body axis.... (Review)
Review
Endodermally derived organs of the gastrointestinal and respiratory system form at distinct anterioposterior and dorsoventral locations along the vertebrate body axis. This stereotyped program of organ formation depends on the correct patterning of the endodermal epithelium so that organ differentiation and morphogenesis occur at appropriate positions along the gut tube. Whereas some initial patterning of the endoderm is known to occur early, during germ-layer formation and gastrulation, later signaling events, originating from a number of adjacent tissue layers, are essential for the development of endodermal organs. Previous studies have shown that signals arising from the notochord are important for patterning of the ectodermally derived floor plate of the neural tube and the mesodermally derived somites. This review will discuss recent evidence indicating that signals arising from the notochord also play a role in regulating endoderm development.
Topics: Body Patterning; Ectoderm; Embryonic Induction; Endoderm; Germ Layers; Mesoderm; Notochord; Pancreas
PubMed: 11356015
DOI: 10.1006/dbio.2001.0214 -
The International Journal of... 2012Hydra is a classic and simple model for pattern formation and regeneration research. More recently, it has also been promoted as a model to study ancestral stem cell... (Review)
Review
Hydra is a classic and simple model for pattern formation and regeneration research. More recently, it has also been promoted as a model to study ancestral stem cell biology. Three independent cell lineages form the body of the polyp and exhibit characteristics of stem cell systems. In order to define differences in stemness between the ectodermal and endodermal epitheliomuscular cell lineages and the interstitial cell lineage, we compare cellular properties and decision making. We argue that these three lineages are expected to show substantial variation in their stemness-related gene regulatory networks. Finally, we discuss Wnt signalling pathways and Myc oncoproteins, which are beginning to offer a perspective on how proliferation and differentiation might be regulated.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Lineage; Ectoderm; Endoderm; Epithelial Cells; Hydra; Morphogenesis; Multipotent Stem Cells; Proto-Oncogene Proteins c-myc; Regeneration; Wnt Signaling Pathway
PubMed: 22689357
DOI: 10.1387/ijdb.113426bh -
Development (Cambridge, England) Oct 2022Directed differentiation of pluripotent stem cells (PSCs) is a powerful model system for deconstructing embryonic development. Although mice are the most advanced...
Directed differentiation of pluripotent stem cells (PSCs) is a powerful model system for deconstructing embryonic development. Although mice are the most advanced mammalian model system for genetic studies of embryonic development, state-of-the-art protocols for directed differentiation of mouse PSCs into defined lineages require additional steps and generates target cell types with lower purity than analogous protocols for human PSCs, limiting their application as models for mechanistic studies of development. Here, we examine the potential of mouse epiblast stem cells cultured in media containing Wnt pathway inhibitors as a starting point for directed differentiation. As a proof of concept, we focused our efforts on two specific cell/tissue types that have proven difficult to generate efficiently and reproducibly from mouse embryonic stem cells: definitive endoderm and neural organoids. We present new protocols for rapid generation of nearly pure definitive endoderm and forebrain-patterned neural organoids that model the development of prethalamic and hippocampal neurons. These differentiation models present new possibilities for combining mouse genetic tools with in vitro differentiation to characterize molecular and cellular mechanisms of embryonic development.
Topics: Animals; Cell Differentiation; Endoderm; Female; Germ Layers; Humans; Mammals; Mice; Organoids; Pluripotent Stem Cells; Pregnancy; Prosencephalon
PubMed: 35899604
DOI: 10.1242/dev.200561 -
Developmental Dynamics : An Official... Nov 2021The trachea is a rigid air duct with some mobility, which comprises the upper region of the respiratory tract and delivers inhaled air to alveoli for gas exchange.... (Review)
Review
The trachea is a rigid air duct with some mobility, which comprises the upper region of the respiratory tract and delivers inhaled air to alveoli for gas exchange. During development, the tracheal primordium is first established at the ventral anterior foregut by interactions between the epithelium and mesenchyme through various signaling pathways, such as Wnt, Bmp, retinoic acid, Shh, and Fgf, and then segregates from digestive organs. Abnormalities in this crosstalk result in lethal congenital diseases, such as tracheal agenesis. Interestingly, these molecular mechanisms also play roles in tissue regeneration in adulthood, although it remains less understood compared with their roles in embryonic development. In this review, we discuss cellular and molecular mechanisms of trachea development that regulate the morphogenesis of this simple tubular structure and identities of individual differentiated cells. We also discuss how the facultative regeneration capacity of the epithelium is established during development and maintained in adulthood.
Topics: Endoderm; Female; Gene Expression Regulation, Developmental; Humans; Mesoderm; Organogenesis; Pregnancy; Trachea
PubMed: 33840142
DOI: 10.1002/dvdy.345 -
Proceedings of the National Academy of... Jun 2021Markers for the endoderm and mesoderm germ layers are commonly expressed together in the early embryo, potentially reflecting cells' ability to explore potential fates...
Markers for the endoderm and mesoderm germ layers are commonly expressed together in the early embryo, potentially reflecting cells' ability to explore potential fates before fully committing. It remains unclear when commitment to a single-germ layer is reached and how it is impacted by external signals. Here, we address this important question in , a convenient model system in which mesodermal and endodermal fates are associated with distinct cellular movements during gastrulation. Systematically applying endoderm-inducing extracellular signal-regulated kinase (ERK) signals to the ventral medial embryo-which normally only receives a mesoderm-inducing cue-reveals a critical time window during which mesodermal cell movements and gene expression are suppressed by proendoderm signaling. We identify the ERK target gene () as the main cause of the ventral furrow suppression and use computational modeling to show that Hkb repression of the mesoderm-associated gene is sufficient to account for a broad range of transcriptional and morphogenetic effects. Our approach, pairing precise signaling perturbations with observation of transcriptional dynamics and cell movements, provides a general framework for dissecting the complexities of combinatorial tissue patterning.
Topics: Animals; DNA-Binding Proteins; Drosophila Proteins; Drosophila melanogaster; Endoderm; Gastrula; Gastrulation; MAP Kinase Signaling System; Mesoderm; Models, Biological
PubMed: 34083443
DOI: 10.1073/pnas.2102691118 -
Developmental Dynamics : An Official... Sep 2006The endoderm is one of the primary germ layers but, in comparison to ectoderm and mesoderm, has received less attention. The definitive endoderm forms during... (Review)
Review
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.
Topics: Animals; Body Patterning; Digestive System; Endoderm; Female; Gastrula; Gene Expression Regulation, Developmental; Head; Mice; Morphogenesis; Mutation; Pregnancy; Stem Cells
PubMed: 16752393
DOI: 10.1002/dvdy.20846 -
Nature Communications Aug 2020The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory...
The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory defects in neonates. Here we show that canonical Wnt signaling in mesoderm is critical to confer trachea mesenchymal identity in human and mouse. At the initiation of tracheal development, endoderm begins to express Nkx2.1, and then mesoderm expresses the Tbx4 gene. Loss of β-catenin in fetal mouse mesoderm causes loss of Tbx4 tracheal mesoderm and tracheal cartilage agenesis. The mesenchymal Tbx4 expression relies on endodermal Wnt activation and Wnt ligand secretion but is independent of known Nkx2.1-mediated respiratory development, suggesting that bidirectional Wnt signaling between endoderm and mesoderm promotes trachea development. Activating Wnt, Bmp signaling in mouse embryonic stem cell (ESC)-derived lateral plate mesoderm (LPM) generates tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation is required along with WNT to generate proper tracheal mesoderm. Together, these findings may contribute to developing applications for human tracheal tissue repair.
Topics: Animals; Cell Differentiation; Cells, Cultured; Endoderm; Gene Expression Regulation, Developmental; Human Embryonic Stem Cells; Humans; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mouse Embryonic Stem Cells; T-Box Domain Proteins; Thyroid Nuclear Factor 1; Trachea; Wnt Signaling Pathway; beta Catenin
PubMed: 32855415
DOI: 10.1038/s41467-020-17969-w -
Philosophical Transactions of the Royal... Dec 2014Despite the importance of the gut and its accessory organs, our understanding of early endoderm development is still incomplete. Traditionally, endoderm has been... (Review)
Review
Despite the importance of the gut and its accessory organs, our understanding of early endoderm development is still incomplete. Traditionally, endoderm has been difficult to study because of its small size and relative fragility. However, recent advances in live cell imaging technologies have dramatically expanded our understanding of this tissue, adding a new appreciation for the complex molecular and morphogenetic processes that mediate gut formation. Several spatially and molecularly distinct subpopulations have been shown to exist within the endoderm before the onset of gastrulation. Here, we review findings that have uncovered complex cell movements within the endodermal layer, before and during gastrulation, leading to the conclusion that cells from primitive endoderm contribute descendants directly to gut.
Topics: Animals; Cell Differentiation; Cell Movement; Endoderm; Gastrointestinal Tract; Mice; Models, Biological; Morphogenesis
PubMed: 25349455
DOI: 10.1098/rstb.2013.0547 -
Comprehensive Physiology Apr 2013Liver is a prime organ responsible for synthesis, metabolism, and detoxification. The organ is endodermal in origin and its development is regulated by temporal,... (Review)
Review
Liver is a prime organ responsible for synthesis, metabolism, and detoxification. The organ is endodermal in origin and its development is regulated by temporal, complex, and finely balanced cellular and molecular interactions that dictate its origin, growth, and maturation. We discuss the relevance of endoderm patterning, which truly is the first step toward mapping of domains that will give rise to specific organs. Once foregut patterning is completed, certain cells within the foregut endoderm gain competence in the form of expression of certain transcription factors that allow them to respond to certain inductive signals. Hepatic specification is then a result of such inductive signals, which often emanate from the surrounding mesenchyme. During hepatic specification bipotential hepatic stem cells or hepatoblasts become apparent and undergo expansion, which results in a visible liver primordium during the stage of hepatic morphogenesis. Hepatoblasts next differentiate into either hepatocytes or cholangiocytes. The expansion and differentiation is regulated by cellular and molecular interactions between hepatoblasts and mesenchymal cells including sinusoidal endothelial cells, stellate cells, and also innate hematopoietic elements. Further maturation of hepatocytes and cholangiocytes continues during late hepatic development as a function of various growth factors. At this time, liver gains architectural novelty in the form of zonality and at cellular level acquires polarity. A comprehensive elucidation of such finely tuned developmental cues have been the basis of transdifferentiation of various types of stem cells to hepatocyte-like cells for purposes of understanding health and disease and for therapeutic applications.
Topics: Animals; Cell Differentiation; Endoderm; Hepatocytes; Humans; Liver; Stem Cells
PubMed: 23720330
DOI: 10.1002/cphy.c120022