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Cell Apr 2001
Review
Topics: Animals; Caenorhabditis elegans; DNA-Binding Proteins; Germ Layers; Morphogenesis; Signal Transduction; Transcription Factors; Transforming Growth Factor beta; Zebrafish
PubMed: 11336666
DOI: 10.1016/s0092-8674(01)00307-5 -
Current Biology : CB Oct 2001Nodal signalling is essential for vertebrate germ-layer formation. How this single signal can generate such a diverse array of tissues remains a mystery and is an area... (Review)
Review
Nodal signalling is essential for vertebrate germ-layer formation. How this single signal can generate such a diverse array of tissues remains a mystery and is an area of intense research. Three recent reports reveal unanticipated subtleties to the process and provide new mechanisms for generating distinct responses.
Topics: Animals; Embryonic Induction; Germ Layers; Models, Biological; Nodal Protein; Receptors, Cell Surface; Signal Transduction; Transforming Growth Factor beta; Vertebrates
PubMed: 11696347
DOI: 10.1016/s0960-9822(01)00522-x -
Nature Aug 2019During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state....
During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state. Concurrently, germ layers are formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mapping and lineage-analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation. The regionalization of cell fates preceding the formation of the basic body plan-the mechanisms of which are instrumental for understanding embryonic programming and stem-cell-based translational study-is conserved in vertebrate embryos. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of the post-implantation embryo has yet to be undertaken. Here we report a spatially resolved transcriptome of cell populations at defined positions in the germ layers during development from pre- to late-gastrulation stages. This spatiotemporal transcriptome provides high-resolution digitized in situ gene-expression profiles, reveals the molecular genealogy of tissue lineages and defines the continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning, supports a role of Hippo-Yap signalling in germ-layer development and reveals the contribution of visceral endoderm to the endoderm in the early mouse embryo.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Cycle Proteins; Cell Differentiation; Cell Lineage; Embryo, Mammalian; Embryonic Development; Gene Expression Regulation, Developmental; Germ Layers; Hippo Signaling Pathway; Mice; Mice, Inbred C57BL; Protein Serine-Threonine Kinases; Regulon; Signal Transduction; Transcriptome; YAP-Signaling Proteins
PubMed: 31391582
DOI: 10.1038/s41586-019-1469-8 -
Proceedings of the National Academy of... Feb 2018Robust morphogenetic events are pivotal for animal embryogenesis. However, comparison of the modes of development of different members of a phylum suggests that the...
Robust morphogenetic events are pivotal for animal embryogenesis. However, comparison of the modes of development of different members of a phylum suggests that the spectrum of developmental trajectories accessible for a species might be far broader than can be concluded from the observation of normal development. Here, by using a combination of microsurgery and transgenic reporter gene expression, we show that, facing a new developmental context, the aggregates of dissociated embryonic cells of the sea anemone take an alternative developmental trajectory. The self-organizing aggregates rely on Wnt signals produced by the cells of the original blastopore lip organizer to form body axes but employ morphogenetic events typical for normal development of distantly related cnidarians to re-establish the germ layers. The reaggregated cells show enormous plasticity including the capacity of the ectodermal cells to convert into endoderm. Our results suggest that new developmental trajectories may evolve relatively easily when highly plastic embryonic cells face new constraints.
Topics: Animals; Biological Evolution; Cell Aggregation; Ectoderm; Embryonic Development; Gene Expression Regulation, Developmental; Germ Layers; Sea Anemones; Signal Transduction; Wnt Proteins
PubMed: 29440382
DOI: 10.1073/pnas.1711516115 -
Lancet (London, England) Oct 2016
Topics: Cartilage; Germ Layers; Humans; Wound Healing
PubMed: 27789004
DOI: 10.1016/S0140-6736(16)31892-X -
Nature Oct 2023The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after...
The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation. Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking. Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs). Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions). Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days after fertilization (Carnegie stage 6a). These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development.
Topics: Humans; Embryo Implantation; Embryo, Mammalian; Embryonic Development; Fertilization; Gastrulation; Germ Layers; Human Embryonic Stem Cells; Trophoblasts; Yolk Sac; Giant Cells
PubMed: 37673118
DOI: 10.1038/s41586-023-06604-5 -
Cellular and Molecular Life Sciences :... Mar 2016In order to generate the tissues and organs of a multicellular organism, different cell types have to be generated during embryonic development. The first step in this... (Review)
Review
In order to generate the tissues and organs of a multicellular organism, different cell types have to be generated during embryonic development. The first step in this process of cellular diversification is the formation of the three germ layers: ectoderm, endoderm and mesoderm. The ectoderm gives rise to the nervous system, epidermis and various neural crest-derived tissues, the endoderm goes on to form the gastrointestinal, respiratory and urinary systems as well as many endocrine glands, and the mesoderm will form the notochord, axial skeleton, cartilage, connective tissue, trunk muscles, kidneys and blood. Classic experiments in amphibian embryos revealed the tissue interactions involved in germ layer formation and provided the groundwork for the identification of secreted and intracellular factors involved in this process. We will begin this review by summarising the key findings of those studies. We will then evaluate them in the light of more recent genetic studies that helped clarify which of the previously identified factors are required for germ layer formation in vivo, and to what extent the mechanisms identified in amphibians are conserved across other vertebrate species. Collectively, these studies have started to reveal the gene regulatory network (GRN) underlying vertebrate germ layer specification and we will conclude our review by providing examples how our understanding of this GRN can be employed to differentiate stem cells in a targeted fashion for therapeutic purposes.
Topics: Animals; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Germ Layers; Humans; Signal Transduction; Stem Cells
PubMed: 26667903
DOI: 10.1007/s00018-015-2092-y -
Development, Growth & Differentiation Jun 2020A single-celled fertilized egg develops into a complex, multicellular animal through a series of selection processes of developmental pathways. During these processes,... (Review)
Review
A single-celled fertilized egg develops into a complex, multicellular animal through a series of selection processes of developmental pathways. During these processes, regulatory genes exhibit spatiotemporally restricted expression under the control of the species-specific genetic program, and dictate developmental processes from germ layer formation to cellular differentiation. Elucidation of molecular mechanisms underlying developmental processes and also of mechanistic bases for morphological diversification during evolution is one of the central issues in contemporary developmental biology. Progress has been made due to recent technological innovations, such as high-throughput nucleotide sequencing, live-cell imaging, efficient genetic manipulation, and establishment of the organoid system, opening new avenues to the above issues.
Topics: Animals; Biological Evolution; Enhancer Elements, Genetic; Gene Expression Regulation, Developmental; Germ Layers
PubMed: 32471018
DOI: 10.1111/dgd.12683 -
Birth Defects Research. Part C, Embryo... Nov 2003The understanding of germ layer formation in vertebrates began with classical experimental embryology. Early in the 20th century, Spemann and Mangold (1924) identified a... (Review)
Review
The understanding of germ layer formation in vertebrates began with classical experimental embryology. Early in the 20th century, Spemann and Mangold (1924) identified a region of the early embryo capable of inducing an entire embryonic axis. Termed the dorsal organizer, the tissue and the activity have been shown to exist in all vertebrates examined. In mice, for example, the activity resides in a region of the gastrula embryo known as the node. Experiments by the Dutch embryologist Nieuwkoop (1967a, 1967b, 1973, 1977) showed that a signal derived from the vegetal half of the amphibian embryo is responsible for the formation of mesoderm. Nieuwkoop's results allowed the development of in vitro assays that led, in the late 1980s and early 1990s, to the identification of growth factors essential for germ layer formation. Through more recent genetic investigations in mice and zebrafish, we now know that one class of secreted growth factor, called Nodal because of its localized expression in the mouse node, is essential for formation of mesoderm and endoderm and for the morphological rearrangements that occur during gastrulation.
Topics: Activins; Animals; Body Patterning; Embryonic Induction; Gastrula; Germ Layers; Inhibin-beta Subunits; Intracellular Signaling Peptides and Proteins; Mesoderm; Mice; Nodal Protein; Nodal Signaling Ligands; Organizers, Embryonic; Signal Transduction; Transforming Growth Factor beta; Vertebrates; Xenopus Proteins; Xenopus laevis; Zebrafish Proteins
PubMed: 14745973
DOI: 10.1002/bdrc.10027 -
Nucleic Acids Research May 2022Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq...
Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Mechanistically, we find that QKI represses inclusion of exon 7 in BIN1 pre-mRNA via an exonic ACUAA motif, and this is concomitant with intron removal and cleavage from chromatin. Collectively, our results uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.
Topics: Alternative Splicing; Cell Differentiation; Cell Lineage; Endoderm; Germ Layers; Heart; Humans; Mesoderm; RNA-Binding Proteins
PubMed: 35544276
DOI: 10.1093/nar/gkac327