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Cells May 2023Elongation of the posterior body axis is distinct from that of the anterior trunk and head. Early drivers of posterior elongation are the neural plate/tube and...
Elongation of the posterior body axis is distinct from that of the anterior trunk and head. Early drivers of posterior elongation are the neural plate/tube and notochord, later followed by the presomitic mesoderm (PSM), together with the neural tube and notochord. In axolotl, posterior neural plate-derived PSM is pushed posteriorly by convergence and extension of the neural plate. The PSM does not go through the blastopore but turns anteriorly to join the gastrulated paraxial mesoderm. To gain a deeper understanding of the process of axial elongation, a detailed characterization of PSM morphogenesis, which precedes somite formation, and of other tissues (such as the epidermis, lateral plate mesoderm and endoderm) is needed. We investigated these issues with specific tissue labelling techniques (DiI injections and GFP tissue grafting) in combination with optical tissue clearing and 3D reconstructions. We defined a spatiotemporal order of PSM morphogenesis that is characterized by changes in collective cell behaviour. The PSM forms a cohesive tissue strand and largely retains this cohesiveness even after epidermis removal. We show that during embryogenesis, the PSM, as well as the lateral plate and endoderm move anteriorly, while the net movement of the axis is posterior.
Topics: Neural Plate; Mesoderm; Morphogenesis; Embryonic Development; Muscles
PubMed: 37174713
DOI: 10.3390/cells12091313 -
Developmental Biology Jun 2007Zic family zinc-finger proteins play various roles in animal development. In mice, five Zic genes (Zic1-5) have been reported. Despite the partly overlapping expression...
Zic family zinc-finger proteins play various roles in animal development. In mice, five Zic genes (Zic1-5) have been reported. Despite the partly overlapping expression profiles of these genes, mouse mutants for each Zic show distinct phenotypes. To uncover possible redundant roles, we characterized Zic2/Zic3 compound mutant mice. Zic2 and Zic3 are both expressed in presomitic mesoderm, forming and newly generated somites with differential spatiotemporal accentuation. Mice heterozygous for the hypomorphic Zic2 allele together with null Zic3 allele generally showed severe malformations of the axial skeleton, including asymmetric or rostro-caudally bridged vertebrae, and reduction of the number of caudal vertebral bones, that are not obvious in single mutants. These defects were preceded by perturbed somitic marker expression, and reduced paraxial mesoderm progenitors in the primitive streak. These results suggest that Zic2 and Zic3 cooperatively control the segmentation of paraxial mesoderm at multiple stages. In addition to the segmentation abnormality, the compound mutant also showed neural tube defects that ran the entire rostro-caudal extent (craniorachischisis), suggesting that neurulation is another developmental process where Zic2 and Zic3 have redundant functions.
Topics: Animals; Bone Development; Cell Proliferation; Embryo, Mammalian; Gastrula; Gene Expression Regulation, Developmental; Genetic Markers; Homeodomain Proteins; Mesoderm; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Neural Crest; Transcription Factors
PubMed: 17490632
DOI: 10.1016/j.ydbio.2007.04.003 -
The International Journal of... 2010The T-box gene VegT plays a crucial role during mesendoderm specification of the amphibian embryo. While the function of maternal VegT (mVegT) has been extensively...
The T-box gene VegT plays a crucial role during mesendoderm specification of the amphibian embryo. While the function of maternal VegT (mVegT) has been extensively investigated, little is known about the function and transcriptional regulation of zygotic VegT (zVegT). In the present study, we used comparative genomics and a knockdown experiment to demonstrate that zVegT is the orthologous gene of zebrafish Spadetail/Tbx16 and chick Tbx6L/Tbx6, and has an essential role in paraxial mesodermal formation. zVegT knockdown embryos show several defects in the patterning of trunk mesoderm, such as abnormal segmentation of somites, a reduction in muscle, and the formation of an abnormal mass of cells at the tail tip. We also identified the cis-regulatory elements of zVegT that are necessary and sufficient for mesoderm-specific expression. These cis-regulatory elements are located in two separate upstream regions of zVegT, corresponding to the first intron of mVegT. The results of in vitro binding and functional assays indicate that Forkhead box H1 (FoxH1) and Eomesodermin (Eomes) are the trans-acting factors required for zVegT expression. Our results highlight the essential role of zVegT in organization of paraxial mesoderm, and reveal that zVegT is regulated by a coherent feedforward loop of Nodal signaling via Eomes.
Topics: Animals; Base Sequence; Blotting, Western; Body Patterning; Chickens; Electrophoretic Mobility Shift Assay; Embryo, Nonmammalian; Female; Gene Expression Regulation; Immunoenzyme Techniques; In Situ Hybridization; Mesoderm; Molecular Sequence Data; Nodal Protein; Promoter Regions, Genetic; Protein Biosynthesis; RNA, Messenger; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; T-Box Domain Proteins; Transcription, Genetic; Xenopus Proteins; Xenopus laevis; Zebrafish; Zygote
PubMed: 20013651
DOI: 10.1387/ijdb.082837mf -
Developmental Biology Oct 1998In vertebrates, the segmented somites, which are the medial-most component in the paraxial mesoderm, are the entity giving rise to the axial bones and skeletal muscles....
In vertebrates, the segmented somites, which are the medial-most component in the paraxial mesoderm, are the entity giving rise to the axial bones and skeletal muscles. We previously demonstrated that the mechanism that distinguishes the somite from the more lateral mesoderm (lateral plate) involves different levels of BMP-4 activity which is highest in the lateral plate. We report that Noggin, an antagonist of BMP-4, is expressed in the presumptive somite and appears to control effective levels of BMP-4 to differentiate somitic mesoderm from the lateral plate. When Noggin-producing cells were implanted into the presumptive lateral plate, they produced ectopic somites that were respecified from the lateral plate precursors. These somites exhibited no mediolateral (M-L) polarity, but acquired it when implanted Noggin was eliminated. Thus, in normal embryogenesis no or low BMP-4 activity realized by Noggin specifies the somites in the medial-most portion of the paraxial mesoderm, and then BMP-4 emanating from the lateral plate subsequently establishes the M-L polarity in the somites.
Topics: Amino Acid Sequence; Animals; Base Sequence; Body Patterning; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; COS Cells; Carrier Proteins; Chickens; DNA Probes; In Situ Hybridization; Mesoderm; Molecular Sequence Data; Proteins; RNA, Messenger; Sequence Homology, Amino Acid; Somites; Transfection; Xenopus; Xenopus Proteins; beta-Galactosidase
PubMed: 9769170
DOI: 10.1006/dbio.1998.8895 -
Stem Cells and Development Jul 2013The vertebrae mesoderm is a source of cells that forms a variety of tissues, including the heart, vasculature, and blood. Consequently, the derivation of various...
The vertebrae mesoderm is a source of cells that forms a variety of tissues, including the heart, vasculature, and blood. Consequently, the derivation of various mesoderm-specific cell types from human embryonic stem cells (hESCs) has attracted the interest of many investigators owing to their therapeutic potential in clinical applications. However, the need for efficient and reliable methods of differentiation into mesoderm lineage cell types remains a significant challenge. Here, we demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3) is an essential first step toward efficient generation of the mesoderm. Under chemically defined conditions without additional growth factors/cytokines, short-term GSK inhibitor (GSKi) treatment effectively drives differentiation of hESCs into the primitive streak (PS), which can potentially commit toward the mesoderm when further supplemented with bone morphogenetic protein 4. Further analysis confirmed that the PS-like cells derived from GSKi treatment are bipotential, being able to specify toward the endoderm as well. Our findings suggest that the bipotential, PS/mesendoderm-like cell population exists only at the initial stages of GSK-3 inhibition, whereas long-term inhibition results in an endodermal fate. Lastly, we demonstrated that our differentiation approach could efficiently generate lateral plate (CD34(+)KDR(+)) and paraxial (CD34(-)PDGFRα(+)) mesoderm subsets that can be further differentiated along the endothelial and smooth muscle lineages, respectively. In conclusion, our study presents a unique approach for generating early mesoderm progenitors in a chemically directed fashion through the use of small-molecule GSK-3 inhibitor, which may be useful for future applications in regenerative medicine.
Topics: Bone Morphogenetic Protein 4; Cell Differentiation; Cell Lineage; Embryonic Stem Cells; Endoderm; Glycogen Synthase Kinase 3; Humans; Mesoderm; Signal Transduction
PubMed: 23413973
DOI: 10.1089/scd.2012.0590 -
Cellular and Molecular Life Sciences :... Oct 2015The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and... (Review)
Review
The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal-epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal-epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal-epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration.
Topics: Cell Communication; Cell Differentiation; Gastrointestinal Tract; Humans; Intestinal Mucosa; Mesoderm; Myocytes, Smooth Muscle; Signal Transduction; Transcription Factors
PubMed: 26126787
DOI: 10.1007/s00018-015-1975-2 -
Stem Cell Research & Therapy Aug 2010Cellular commitment during vertebrate embryogenesis is controlled by an interplay of intrinsic regulators and morphogenetic signals. These mechanisms recruit a subset of... (Review)
Review
Cellular commitment during vertebrate embryogenesis is controlled by an interplay of intrinsic regulators and morphogenetic signals. These mechanisms recruit a subset of cells in the developing organism to become the ancestors of skeletal muscle. Signals that control progression through the myogenic lineage converge on a battery of hierarchically organized transcription factors which modulate the cells to either remain in a primitive state or allow their commitment and differentiation into skeletal muscle fibers. A small population of cells will retain a largely unspecified state throughout development. Such stem cells, in conjunction with more committed myogenic progenitors, form a heterogeneous population that colonizes adult skeletal muscle as satellite cells. The satellite cell pool is responsible for the remarkable regenerative capacity of skeletal muscle. Similar to their counterparts during embryonic development, satellite cells are capable of self-renewal and can give rise to myogenic progeny. Impaired satellite cell homeostasis has been associated with numerous muscular disorders. Due to intense research efforts in the past two decades, the complex biology of muscle stem cells has now revealed some of its secrets and new avenues for the development of therapeutic molecules have emerged. In the present review we focus on the extrinsic mechanisms that control self-renewal, specification and differentiation of satellite cells and their significance for the development of biologic drugs.
Topics: Cell Differentiation; Humans; Intercellular Signaling Peptides and Proteins; Mesoderm; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Signal Transduction; Stem Cell Niche
PubMed: 20804582
DOI: 10.1186/scrt27 -
Genes & Development Dec 2000Paraxial mesoderm in vertebrates gives rise to all trunk and limb skeletal muscles, the trunk skeleton, and portions of the trunk dermis and vasculature. We show here...
Paraxial mesoderm in vertebrates gives rise to all trunk and limb skeletal muscles, the trunk skeleton, and portions of the trunk dermis and vasculature. We show here that germline deletion of mouse pMesogenin1, a bHLH class gene specifically expressed in developmentally immature unsegmented paraxial mesoderm, causes complete failure of somite formation and segmentation of the body trunk and tail. At the molecular level, the phenotype features dramatic loss of expression within the presomitic mesoderm of Notch/Delta pathway components and oscillating somitic clock genes that are thought to control segmentation and somitogenesis. Subsequent patterning and specification steps for paraxial mesoderm also fail, leading to a complete absence of all trunk paraxial mesoderm derivatives, which include skeletal muscle, vertebrae, and ribs. We infer that pMesogenin1 is an essential upstream regulator of trunk paraxial mesoderm development and segmentation.
Topics: Abnormalities, Multiple; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Embryonic and Fetal Development; Female; Fetal Proteins; Fungal Proteins; Gene Expression Regulation, Developmental; Glycosyltransferases; Helix-Loop-Helix Motifs; Homozygote; Male; Membrane Proteins; Mesoderm; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Proteins; Receptors, Notch; Recombination, Genetic; Saccharomyces cerevisiae Proteins; Signal Transduction; T-Box Domain Proteins; Tail; Transcription Factors
PubMed: 11124811
DOI: 10.1101/gad.850000 -
Biophysical Journal Jul 2013The invagination of the mesoderm in the Drosophila melanogaster embryo is an intensely studied example of epithelial folding. Several theoretical studies have explored... (Review)
Review
The invagination of the mesoderm in the Drosophila melanogaster embryo is an intensely studied example of epithelial folding. Several theoretical studies have explored the conditions and mechanisms needed to reproduce the formation of the invagination in silico. Here we discuss the aspects of epithelial folding captured by these studies, and compare the questions addressed, the approaches used, and the answers provided.
Topics: Animals; Biomechanical Phenomena; Biophysical Phenomena; Drosophila melanogaster; Embryo, Nonmammalian; Mesoderm; Models, Biological
PubMed: 23823218
DOI: 10.1016/j.bpj.2013.05.039 -
PLoS Biology Aug 2014Cells of the spinal cord and somites arise from shared, dual-fated precursors, located towards the posterior of the elongating embryo. Here we show that these...
Cells of the spinal cord and somites arise from shared, dual-fated precursors, located towards the posterior of the elongating embryo. Here we show that these neuromesodermal progenitors (NMPs) can readily be generated in vitro from mouse and human pluripotent stem cells by activating Wnt and Fgf signalling, timed to emulate in vivo development. Similar to NMPs in vivo, these cells co-express the neural factor Sox2 and the mesodermal factor Brachyury and differentiate into neural and paraxial mesoderm in vitro and in vivo. The neural cells produced by NMPs have spinal cord but not anterior neural identity and can differentiate into spinal cord motor neurons. This is consistent with the shared origin of spinal cord and somites and the distinct ontogeny of the anterior and posterior nervous system. Systematic analysis of the transcriptome during differentiation identifies the molecular correlates of each of the cell identities and the routes by which they are obtained. Moreover, we take advantage of the system to provide evidence that Brachyury represses neural differentiation and that signals from mesoderm are not necessary to induce the posterior identity of spinal cord cells. This indicates that the mesoderm inducing and posteriorising functions of Wnt signalling represent two molecularly separate activities. Together the data illustrate how reverse engineering normal developmental mechanisms allows the differentiation of specific cell types in vitro and the analysis of previous difficult to access aspects of embryo development.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Line; Chick Embryo; Embryonic Stem Cells; Fetal Proteins; Fibroblast Growth Factors; Germ Layers; Humans; Mesoderm; Mice; Neural Stem Cells; Spinal Cord; T-Box Domain Proteins; Transcription, Genetic; Wnt Signaling Pathway
PubMed: 25157815
DOI: 10.1371/journal.pbio.1001937