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Cells Aug 2021Fibroblast growth factors (FGFs) comprise a large family of growth factors, regulating diverse biological processes including cell proliferation, migration, and... (Review)
Review
Fibroblast growth factors (FGFs) comprise a large family of growth factors, regulating diverse biological processes including cell proliferation, migration, and differentiation. Each FGF binds to a set of FGF receptors to initiate certain intracellular signaling molecules. Accumulated evidence suggests that in early development and adult state of vertebrates, FGFs also play exclusive and context dependent roles. Although FGFs have been the focus of research for therapeutic approaches in cancer, cardiovascular disease, and metabolic syndrome, in this review, we mainly focused on their role in germ layer specification and axis patterning during early vertebrate embryogenesis. We discussed the functional roles of FGFs and their interacting partners as part of the gene regulatory network for germ layer specification, dorsal-ventral (DV), and anterior-posterior (AP) patterning. Finally, we briefly reviewed the regulatory molecules and pharmacological agents discovered that may allow modulation of FGF signaling in research.
Topics: Animals; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Germ Layers; Humans; Models, Biological; Protein Binding; Receptors, Fibroblast Growth Factor; Signal Transduction; Vertebrates
PubMed: 34440915
DOI: 10.3390/cells10082148 -
Seminars in Cell & Developmental Biology Dec 2015During embryonic development, tissues deform by a succession and combination of morphogenetic processes. Tissue compaction is the morphogenetic process by which a tissue... (Review)
Review
During embryonic development, tissues deform by a succession and combination of morphogenetic processes. Tissue compaction is the morphogenetic process by which a tissue adopts a tighter structure. Recent studies characterized the respective roles of cells' adhesive and contractile properties in tissue compaction. In this review, we formalize the mechanical and molecular principles of tissue compaction and we analyze through the prism of this framework several morphogenetic events: the compaction of the early mouse embryo, the formation of the fly retina, the segmentation of somites and the separation of germ layers during gastrulation.
Topics: Animals; Body Patterning; Cell Adhesion; Cell Communication; Embryonic Development; Gastrulation; Germ Layers; Humans; Mechanical Phenomena; Models, Biological
PubMed: 26256955
DOI: 10.1016/j.semcdb.2015.08.001 -
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 -
Mechanisms of Development Nov 2015Non-coding sequences of frog embryo endoderm poly (A+) nuclear RNA are AU-enriched, as compared to those of ectoderm and mesoderm. Endoderm blastomeres contain much less... (Review)
Review
Non-coding sequences of frog embryo endoderm poly (A+) nuclear RNA are AU-enriched, as compared to those of ectoderm and mesoderm. Endoderm blastomeres contain much less H1 histone than is present in ectoderm and mesoderm. H1 histone preferentially binds AT-rich DNA sequences to repress their transcription. The AT-enrichment of non-coding DNA sequences transcribed into poly (A+) nuclear RNA, as well as the low amount of H1 histone, may contribute to the higher transcription frequency of mRNA of endoderm, as compared to that of ectoderm and mesoderm. A greater accumulation of H1 histone in presumptive mesoderm and ectoderm may prevent transcription of endoderm specifying genes in mesoderm and ectoderm. Experimental upregulation of various transcription factors (TFs) can redirect germ layer fate. Most of these TFs bind AT-rich consensus sequences in DNA, suggesting that H1 histone and TFs active during germ layer determination are binding similar sequences.
Topics: AT Rich Sequence; Animals; Base Composition; Binding Sites; Chromatin; DNA; Gene Expression Regulation, Developmental; Germ Layers; Humans; RNA, Messenger; Regulatory Sequences, Ribonucleic Acid; Transcription Factors; Xenopus; Xenopus Proteins
PubMed: 26506258
DOI: 10.1016/j.mod.2015.10.004 -
Cells & Development Dec 2021Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so... (Review)
Review
Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so named because early specification produces cells that often have been observed to simultaneously express both early endoderm and mesoderm transcription factors. Experiments with these cells demonstrate that their progeny can directed entirely toward endoderm or mesoderm, whereas normally they establish both germ layers. This review examines the mechanisms that initiate the conditional endomesoderm state, its metastability, and the mechanisms that resolve that state into definitive endoderm and mesoderm.
Topics: Animals; Embryo, Nonmammalian; Endoderm; Mesoderm; Sea Urchins; Signal Transduction
PubMed: 34610899
DOI: 10.1016/j.cdev.2021.203731 -
Trends in Cell Biology Feb 2022The endoderm, one of the three primary germ layers, gives rise to lung, liver, stomach, intestine, colon, pancreas, bladder, and thyroid. These endoderm-originated... (Review)
Review
The endoderm, one of the three primary germ layers, gives rise to lung, liver, stomach, intestine, colon, pancreas, bladder, and thyroid. These endoderm-originated organs are subject to many life-threatening diseases. However, primary cells/tissues from endodermal organs are often difficult to grow in vitro. Human pluripotent stem cells (hPSCs), therefore, hold great promise for generating endodermal cells and their derivatives for the development of new therapeutics against these human diseases. Although a wealth of research has provided crucial information on the mechanisms underlying endoderm differentiation from hPSCs, increasing evidence has shown that metabolism, in connection with epigenetics, actively regulates endoderm differentiation in addition to the conventional endoderm inducing signals. Here we review recent advances in metabolic and epigenetic regulation of endoderm differentiation.
Topics: Cell Differentiation; Endoderm; Epigenesis, Genetic; Humans; Pluripotent Stem Cells
PubMed: 34607773
DOI: 10.1016/j.tcb.2021.09.002 -
Development (Cambridge, England) Dec 2021Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear...
Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment. We show that the combination of activin A, fibroblast growth factor and the Wnt inhibitor XAV939 (AFX) supports establishment and continuous expansion of pluripotent stem cell lines from porcine, ovine and bovine embryos. Germ layer differentiation was evident in teratomas and readily induced in vitro. Global transcriptome analyses highlighted commonality in transcription factor expression across the three species, while global comparison with porcine embryo stages showed proximity to bilaminar disc epiblast. Clonal genetic manipulation and gene targeting were exemplified in porcine stem cells. We further demonstrated that genetically modified AFX stem cells gave rise to cloned porcine foetuses by nuclear transfer. In summary, for major livestock mammals, pluripotent stem cells related to the formative embryonic disc are reliably established using a common and defined signalling environment. This article has an associated 'The people behind the papers' interview.
Topics: Animals; Cattle; Cell Differentiation; Embryo, Mammalian; Germ Layers; Livestock; Pluripotent Stem Cells; Sheep; Species Specificity; Swine
PubMed: 34874452
DOI: 10.1242/dev.199901 -
EMBO Reports Sep 2022Pluripotent cells in mouse embryos, which first emerge in the inner cell mass of the blastocyst, undergo gradual transition marked by changes in gene expression,... (Review)
Review
Pluripotent cells in mouse embryos, which first emerge in the inner cell mass of the blastocyst, undergo gradual transition marked by changes in gene expression, developmental potential, polarity, and morphology as they develop from the pre-implantation until post-implantation gastrula stage. Recent studies of cultured mouse pluripotent stem cells (PSCs) have clarified the presence of intermediate pluripotent stages between the naïve pluripotent state represented by embryonic stem cells (ESCs-equivalent to the pre-implantation epiblast) and the primed pluripotent state represented by epiblast stem cells (EpiSCs-equivalent to the late post-implantation gastrula epiblast). In this review, we discuss these recent findings in light of our knowledge on peri-implantation mouse development and consider the implications of these new PSCs to understand their temporal sequence and the feasibility of using them as model system for pluripotency.
Topics: Animals; Blastocyst; Cell Differentiation; Embryonic Stem Cells; Germ Layers; Mice; Pluripotent Stem Cells
PubMed: 35903955
DOI: 10.15252/embr.202255010 -
Developmental Biology May 2015The epiblast is a single cell-layered epithelium which generates through gastrulation all tissues in an amniote embryo proper. Specification of the epiblast as a cell... (Review)
Review
The epiblast is a single cell-layered epithelium which generates through gastrulation all tissues in an amniote embryo proper. Specification of the epiblast as a cell lineage in early development is coupled with that of the trophoblast and hypoblast, two lineages dedicated to forming extramebryonic tissues. The complex relationship between molecular specification and morphogenetic segregation of these three lineages is not well understood. In this review I will compare the ontogeny of epithelial epiblast in different amniote groups and emphasize the diversity in cell biological mechanisms employed by each group to reach this conserved epithelial structure as the pre-requisite for gastrulation. The limitations of associating cell fate with cell shape and position will also be discussed. In most amniote groups, bi-potential precursors for the epiblast and hypoblast, similar to the inner cell mass in the eutherian mammals, are not associated with an apolar, inside location in the blastocyst. Conversely, a blastocyst cell with epithelial morphology and superficial location is not indicative of its trophoblast fate. The polar trophoblast is absent in all amniotes except for the eutherian mammals. In the avian, reptilian and eutherian groups, epithelialization of the epiblast occurs after its fate specification and involves a mesenchymal-to-epithelial transition (MET) process, whereas in the monotremes and marsupials, pre-epiblast cells adopt an epithelial morphology prior to their commitment to the epiblast fate. The conservation of an epithelialized epiblast is viewed as an adaptation to evolutionary constraints placed on pre-gastrulation ectoderm in the ancestral amniote. The relationship between epiblast MET and epiblast pluripontency will also be discussed. Whether such an MET/epithelialization process is advantageous for the self-renewal and/or differentiation of human epiblast stem cells in vitro is unclear.
Topics: Animals; Birds; Cell Polarity; Cell Transdifferentiation; Embryonic Development; Epithelium; Germ Layers; Humans; Mammals; Mesoderm; Models, Biological; Morphogenesis; Reptiles; Species Specificity; Trophoblasts
PubMed: 25446532
DOI: 10.1016/j.ydbio.2014.10.003 -
Genes Aug 2022Pluripotent stem cells (PSCs), which can self-renew and give rise to all cell types in all three germ layers, have great potential in regenerative medicine. Recent... (Review)
Review
Pluripotent stem cells (PSCs), which can self-renew and give rise to all cell types in all three germ layers, have great potential in regenerative medicine. Recent studies have shown that PSCs can have three distinct but interrelated pluripotent states: naive, formative, and primed. The PSCs of each state are derived from different stages of the early developing embryo and can be maintained in culture by different molecular mechanisms. In this review, we summarize the current understanding on features of the three pluripotent states and review the underlying molecular mechanisms of maintaining their identities. Lastly, we discuss the interrelation and transition among these pluripotency states. We believe that comprehending the divergence of pluripotent states is essential to fully harness the great potential of stem cells in regenerative medicine.
Topics: Animals; Embryo, Mammalian; Germ Layers; Humans; Mice; Pluripotent Stem Cells; Regenerative Medicine; Signal Transduction
PubMed: 36011370
DOI: 10.3390/genes13081459