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Seminars in Cell & Developmental Biology Jun 2017Germ layer formation is among the earliest differentiation events in metazoan embryos. In triploblasts, three germ layers are formed, among which the endoderm gives rise... (Review)
Review
Germ layer formation is among the earliest differentiation events in metazoan embryos. In triploblasts, three germ layers are formed, among which the endoderm gives rise to the epithelial lining of the gut tube and associated organs including the liver, pancreas and lungs. In frogs (Xenopus), where early germ layer formation has been studied extensively, the process of endoderm specification involves the interplay of dozens of transcription factors. Here, we review the interactions between these factors, summarized in a transcriptional gene regulatory network (GRN). We highlight regulatory connections conserved between frog, fish, mouse, and human endodermal lineages. Especially prominent is the conserved role and regulatory targets of the Nodal signaling pathway and the T-box transcription factors, Vegt and Eomes. Additionally, we highlight network topologies and motifs, and speculate on their possible roles in development.
Topics: Animals; Cell Differentiation; Endoderm; Gene Regulatory Networks; Transcription Factors; Xenopus; Xenopus Proteins
PubMed: 28341363
DOI: 10.1016/j.semcdb.2017.03.003 -
Cell Stem Cell Apr 2018The liver, lung, pancreas, and digestive tract all originate from the endoderm germ layer, and these vital organs are subject to many life-threatening diseases affecting... (Review)
Review
The liver, lung, pancreas, and digestive tract all originate from the endoderm germ layer, and these vital organs are subject to many life-threatening diseases affecting millions of patients. However, primary cells from endodermal organs are often difficult to grow in vitro. Human pluripotent stem cells thus hold great promise for generating endoderm cells and their derivatives as tools for the development of new therapeutics against a variety of global healthcare challenges. Here we describe recent advances in methods for generating endodermal cell types from human pluripotent stem cells and their use for disease modeling and cell-based therapy.
Topics: Endoderm; Humans; Models, Biological; Pluripotent Stem Cells
PubMed: 29625066
DOI: 10.1016/j.stem.2018.03.016 -
Developmental Biology Dec 2018Wilhelm His (1831-1904) provided lasting insights into the development of the central and peripheral nervous system using innovative technologies such as the microtome,... (Review)
Review
Wilhelm His (1831-1904) provided lasting insights into the development of the central and peripheral nervous system using innovative technologies such as the microtome, which he invented. 150 years after his resurrection of the classical germ layer theory of Wolff, von Baer and Remak, his description of the developmental origin of cranial and spinal ganglia from a distinct cell population, now known as the neural crest, has stood the test of time and more recently sparked tremendous advances regarding the molecular development of these important cells. In addition to his 1868 treatise on 'Zwischenstrang' (now neural crest), his work on the development of the human hindbrain published in 1890 provided novel ideas that more than 100 years later form the basis for penetrating molecular investigations of the regionalization of the hindbrain neural tube and of the migration and differentiation of its constituent neuron populations. In the first part of this review we briefly summarize the major discoveries of Wilhelm His and his impact on the field of embryology. In the second part we relate His' observations to current knowledge about the molecular underpinnings of hindbrain development and evolution. We conclude with the proposition, present already in rudimentary form in the writings of His, that a primordial spinal cord-like organization has been molecularly supplemented to generate hindbrain 'neomorphs' such as the cerebellum and the auditory and vestibular nuclei and their associated afferents and sensory organs.
Topics: Animals; Biological Evolution; Body Patterning; Cell Differentiation; Cerebellum; Ganglia, Spinal; Germ Layers; History, 17th Century; History, 18th Century; Humans; Neural Crest; Neural Tube; Neurons; Organogenesis; Rhombencephalon
PubMed: 29447907
DOI: 10.1016/j.ydbio.2018.02.001 -
Philosophical Transactions of the Royal... Dec 2022The blastocyst is a conserved stage and distinct milestone in the development of the mammalian embryo. Blastocyst stage embryos comprise three cell lineages which arise... (Review)
Review
The blastocyst is a conserved stage and distinct milestone in the development of the mammalian embryo. Blastocyst stage embryos comprise three cell lineages which arise through two sequential binary cell fate specification steps. In the first, extra-embryonic trophectoderm (TE) cells segregate from inner cell mass (ICM) cells. Subsequently, ICM cells acquire a pluripotent epiblast (Epi) or extra-embryonic primitive endoderm (PrE, also referred to as hypoblast) identity. In the mouse, nascent Epi and PrE cells emerge in a salt-and-pepper distribution in the early blastocyst and are subsequently sorted into adjacent tissue layers by the late blastocyst stage. Epi cells cluster at the interior of the ICM, while PrE cells are positioned on its surface interfacing the blastocyst cavity, where they display apicobasal polarity. As the embryo implants into the maternal uterus, cells at the periphery of the PrE epithelium, at the intersection with the TE, break away and migrate along the TE as they mature into parietal endoderm (ParE). PrE cells remaining in association with the Epi mature into visceral endoderm. In this review, we discuss our current understanding of the PrE from its specification to its maturation. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.
Topics: Animals; Blastocyst; Cell Differentiation; Cell Lineage; Endoderm; Female; Germ Layers; Mammals; Mice
PubMed: 36252215
DOI: 10.1098/rstb.2021.0252 -
Proceedings of the National Academy of... Sep 2017Germ-layer formation during gastrulation is both a fundamental step of development and a paradigm for tissue formation and remodeling. However, the cellular and...
Germ-layer formation during gastrulation is both a fundamental step of development and a paradigm for tissue formation and remodeling. However, the cellular and molecular basis of germ-layer segregation is poorly understood, mostly because of the lack of direct in vivo observations. We used mosaic zebrafish embryos to investigate the formation of the endoderm. High-resolution live imaging and functional analyses revealed that endodermal cells reach their characteristic innermost position through an active, oriented, and actin-based migration dependent on Rac1, which contrasts with the previously proposed differential adhesion cell sorting. Rather than being attracted to their destination, the yolk syncytial layer, cells appear to migrate away from their neighbors. This migration depends on N-cadherin that, when imposed in ectodermal cells, is sufficient to trigger their internalization without affecting their fate. Overall, these results lead to a model of germ-layer formation in which, upon N-cadherin expression, endodermal cells actively migrate away from their epiblastic neighbors to reach their internal position, revealing cell-contact avoidance as an unexplored mechanism driving germ-layer formation.
Topics: Actin-Related Protein 2-3 Complex; Animals; Cadherins; Cell Movement; Cytoskeleton; Endoderm; Zebrafish; rac1 GTP-Binding Protein
PubMed: 28874564
DOI: 10.1073/pnas.1708116114 -
Genes Nov 2019During vertebrate embryogenesis, precise regulation of gene expression is crucial for proper cell fate determination. Much of what we know about vertebrate development... (Review)
Review
During vertebrate embryogenesis, precise regulation of gene expression is crucial for proper cell fate determination. Much of what we know about vertebrate development has been gleaned from experiments performed on embryos of the amphibian ; this review will focus primarily on studies of this model organism. An early critical step during vertebrate development is the formation of the three primary germ layers-ectoderm, mesoderm, and endoderm-which emerge during the process of gastrulation. While much attention has been focused on the induction of mesoderm and endoderm, it has become clear that differentiation of the ectoderm involves more than the simple absence of inductive cues; rather, it additionally requires the inhibition of mesendoderm-promoting genes. This review aims to summarize our current understanding of the various inhibitors of inappropriate gene expression in the presumptive ectoderm.
Topics: Animals; Cell Differentiation; Ectoderm; Endoderm; Gastrulation; Gene Expression Regulation, Developmental; Germ Layers; Mesoderm; Xenopus laevis
PubMed: 31698780
DOI: 10.3390/genes10110895 -
Current Opinion in Genetics &... Dec 2023The primitive endoderm (PrE, also named hypoblast), a predominantly extraembryonic epithelium that arises from the inner cell mass (ICM) of the mammalian... (Review)
Review
The primitive endoderm (PrE, also named hypoblast), a predominantly extraembryonic epithelium that arises from the inner cell mass (ICM) of the mammalian pre-implantation blastocyst, plays a fundamental role in embryonic development, giving rise to the yolk sac, establishing the anterior-posterior axis and contributing to the gut. PrE is specified from the ICM at the same time as the epiblast (Epi) that will form the embryo proper. While in vitro cell lines resembling the pluripotent Epi have been derived from a variety of conditions, only one model system currently exists for the PrE, naïve extraembryonic endoderm (nEnd). As a result, considerably more is known about the gene regulatory networks and signalling requirements of pluripotent stem cells than nEnd. In this review, we describe the ontogeny and differentiation of the PrE or hypoblast in mouse and primate and then discuss in vitro cell culture models for different extraembryonic endodermal cell types.
Topics: Pregnancy; Female; Humans; Mice; Animals; Endoderm; Germ Layers; Cell Differentiation; Embryo, Mammalian; Blastocyst; Mammals
PubMed: 37783145
DOI: 10.1016/j.gde.2023.102115 -
International Journal of Molecular... Aug 2023Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are isolated from Wharton's jelly tissue of umbilical cords. They possess the ability to differentiate into... (Review)
Review
Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are isolated from Wharton's jelly tissue of umbilical cords. They possess the ability to differentiate into lineage cells of three germ layers. WJ-MSCs have robust proliferative ability and strong immune modulation capacity. They can be easily collected and there are no ethical problems associated with their use. Therefore, WJ-MSCs have great tissue engineering value and clinical application prospects. The identity and functions of WJ-MSCs are regulated by multiple interrelated regulatory mechanisms, including transcriptional regulation and epigenetic modifications. In this article, we summarize the latest research progress on the genetic/epigenetic regulation mechanisms and essential signaling pathways that play crucial roles in pluripotency and differentiation of WJ-MSCs.
Topics: Epigenesis, Genetic; Wharton Jelly; Cell Differentiation; Mesenchymal Stem Cells; Germ Layers
PubMed: 37629090
DOI: 10.3390/ijms241612909 -
International Journal of Molecular... Sep 2016Pigs have great potential to provide preclinical models for human disease in translational research because of their similarities with humans. In this regard, porcine... (Review)
Review
Pigs have great potential to provide preclinical models for human disease in translational research because of their similarities with humans. In this regard, porcine pluripotent cells, which are able to differentiate into cells of all three primary germ layers, might be a suitable animal model for further development of regenerative medicine. Here, we describe the current state of knowledge on apoptosis in pluripotent cells including inner cell mass (ICM), epiblast, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Information is focused on the apoptotic phenomenon in pluripotency, maintenance, and differentiation of pluripotent stem cells and reprogramming of somatic cells in pigs. Additionally, this review examines the multiple roles of apoptosis and summarizes recent progress in porcine pluripotent cells.
Topics: Animals; Apoptosis; Blastocyst Inner Cell Mass; Cell Differentiation; Cellular Reprogramming; Embryonic Stem Cells; Germ Layers; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Regenerative Medicine; Swine
PubMed: 27626414
DOI: 10.3390/ijms17091533 -
Nature Cell Biology Dec 2014Gastrulation leads to three germ layers--ectoderm, mesoderm and endoderm--that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm...
Gastrulation leads to three germ layers--ectoderm, mesoderm and endoderm--that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm results from the widespread intercalation of cells of two distinct origins: pluripotent epiblast-derived definitive endoderm (DE) and extra-embryonic visceral endoderm (VE). Here we image the trajectory of prospective DE cells before intercalating into the VE epithelium. We show that the transcription factor SOX17, which is activated in prospective DE cells before intercalation, is necessary for gut endoderm morphogenesis and the assembly of the basement membrane that separates gut endoderm from mesoderm. Our results mechanistically link gut endoderm morphogenesis and germ layer segregation, two central and conserved features of gastrulation.
Topics: Animals; Basement Membrane; Cadherins; Cell Differentiation; Embryo, Mammalian; Endoderm; Epithelium; Extracellular Matrix; Extracellular Matrix Proteins; Fibronectins; Gastrulation; Germ Layers; Green Fluorescent Proteins; HMGB Proteins; Hepatocyte Nuclear Factor 3-beta; Mesoderm; Mice; Mice, Transgenic; Morphogenesis; Optical Imaging; SOXF Transcription Factors
PubMed: 25419850
DOI: 10.1038/ncb3070