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Cells & Development Dec 2021In vertebrate embryos the presomitic mesoderm becomes progressively segmented into somites at the anterior end while extending along the anterior-posterior axis. A...
In vertebrate embryos the presomitic mesoderm becomes progressively segmented into somites at the anterior end while extending along the anterior-posterior axis. A commonly adopted model to explain how this tissue elongates is that of posterior growth, driven in part by the addition of new cells from uncommitted progenitor populations in the tailbud. However, in zebrafish, much of somitogenesis is associated with an absence of overall volume increase, and posterior progenitors do not contribute new cells until the final stages of somitogenesis. Here, we perform a comprehensive 3D morphometric analysis of the paraxial mesoderm and reveal that extension is linked to a volumetric decrease and an increase in cell density. We also find that individual cells decrease in volume over successive somite stages. Live cell tracking confirms that much of this tissue deformation occurs within the presomitic mesoderm progenitor zone and is associated with non-directional rearrangement. Taken together, we propose a compaction-extension mechanism of tissue elongation that highlights the need to better understand the role tissue intrinsic and extrinsic forces in regulating morphogenesis.
Topics: Animals; Embryonic Development; Mesoderm; Morphogenesis; Somites; Zebrafish
PubMed: 34597846
DOI: 10.1016/j.cdev.2021.203748 -
Genes & Development Sep 2004The vertebral column is derived from somites formed by segmentation of presomitic mesoderm, a fundamental process of vertebrate embryogenesis. Models on the mechanism... (Review)
Review
The vertebral column is derived from somites formed by segmentation of presomitic mesoderm, a fundamental process of vertebrate embryogenesis. Models on the mechanism controlling this process date back some three to four decades. Access to understanding the molecular control of somitogenesis has been gained only recently by the discovery of molecular oscillators (segmentation clock) and gradients of signaling molecules, as predicted by early models. The Notch signaling pathway is linked to the oscillator and plays a decisive role in inter- and intrasomitic boundary formation. An Fgf8 signaling gradient is involved in somite size control. And the (canonical) Wnt signaling pathway, driven by Wnt3a, appears to integrate clock and gradient in a global mechanism controlling the segmentation process. In this review, we discuss recent advances in understanding the molecular mechanism controlling somitogenesis.
Topics: Animals; Biological Clocks; Body Patterning; Fibroblast Growth Factor 8; Fibroblast Growth Factors; Membrane Proteins; Models, Biological; Proto-Oncogene Proteins; Receptors, Notch; Signal Transduction; Somites; Vertebrates; Wnt Proteins
PubMed: 15342488
DOI: 10.1101/gad.1217404 -
Wiley Interdisciplinary Reviews. RNA Jan 2023Biological time keeping, or the duration and tempo at which biological processes occur, is a phenomenon that drives dynamic molecular and morphological changes that... (Review)
Review
Biological time keeping, or the duration and tempo at which biological processes occur, is a phenomenon that drives dynamic molecular and morphological changes that manifest throughout many facets of life. In some cases, the molecular mechanisms regulating the timing of biological transitions are driven by genetic oscillations, or periodic increases and decreases in expression of genes described collectively as a "molecular clock." In vertebrate animals, molecular clocks play a crucial role in fundamental patterning and cell differentiation processes throughout development. For example, during early vertebrate embryogenesis, the segmentation clock regulates the patterning of the embryonic mesoderm into segmented blocks of tissue called somites, which later give rise to axial skeletal muscle and vertebrae. Segmentation clock oscillations are characterized by rapid cycles of mRNA and protein expression. For segmentation clock oscillations to persist, the transcript and protein molecules of clock genes must be short-lived. Faithful, rhythmic, genetic oscillations are sustained by precise regulation at many levels, including post-transcriptional regulation, and such mechanisms are essential for proper vertebrate development. This article is categorized under: RNA Export and Localization > RNA Localization RNA Turnover and Surveillance > Regulation of RNA Stability Translation > Regulation.
Topics: Animals; Biological Clocks; Vertebrates; Somites; RNA; Gene Expression; Gene Expression Regulation, Developmental
PubMed: 35851751
DOI: 10.1002/wrna.1751 -
Developmental Biology Mar 2011Zic genes encode a conserved family of zinc finger proteins with essential functions in neural development and axial skeletal patterning in the vertebrate embryo. Zic...
Zic genes encode a conserved family of zinc finger proteins with essential functions in neural development and axial skeletal patterning in the vertebrate embryo. Zic proteins also function as Gli co-factors in Hedgehog signaling. Here, we report that Zic genes have a role in Myf5 regulation for epaxial somite myogenesis in the mouse embryo. In situ hybridization studies show that Zic1, 2, and 3 transcripts are expressed in Myf5-expressing epaxial myogenic progenitors in the dorsal medial dermomyotome of newly forming somites, and immunohistological studies show that Zic2 protein is co-localized with Myf5 and Pax3 in the dorsal medial lip of the dermomyotome, but is not expressed in the forming myotome. In functional reporter assays, Zic1 and Zic2, but not Zic3, potentiate the transactivation of Gli-dependent Myf5 epaxial somite-specific (ES) enhancer activity in 3T3 cells, and Zic1 activates endogenous Myf5 expression in 10T1/2 cells and in presomitic mesoderm explants. Zic2 also co-immunoprecipitates with Gli2, indicating that Zic2 forms complexes with Gli2 to promote Myf5 expression. Genetic studies show that, although Zic2 and Zic1 are activated normally in sonic hedgehog(-/-) mutant embryos, Myf5 expression in newly forming somites is deficient in both sonic hedgehog(-/-) and in Zic2(kd/kd) mutant mouse embryos, providing further evidence that these Zic genes are upstream regulators of Hedgehog-mediated Myf5 activation. Myf5 activation in newly forming somites is delayed in Zic2 mutant embryos until the time of Zic1 activation, and both Zic2 and Myf5 require noggin for their activation.
Topics: Animals; Gene Expression Regulation, Developmental; Hedgehog Proteins; Mice; Muscle Development; MyoD Protein; Myogenic Regulatory Factor 5; NIH 3T3 Cells; Somites; Transcription Factors
PubMed: 21211521
DOI: 10.1016/j.ydbio.2010.12.037 -
Developmental Biology Jun 2023Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although the...
Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although the function of fibroblasts has been extensively studied in adults, the embryonic origin and diversification of different fibroblast subtypes during development remain largely unexplored. Using zebrafish as a model, we show that the sclerotome, a sub-compartment of the somite, is the embryonic source of multiple fibroblast subtypes including tenocytes (tendon fibroblasts), blood vessel associated fibroblasts, fin mesenchymal cells, and interstitial fibroblasts. High-resolution imaging shows that different fibroblast subtypes occupy unique anatomical locations with distinct morphologies. Long-term Cre-mediated lineage tracing reveals that the sclerotome also contributes to cells closely associated with the axial skeleton. Ablation of sclerotome progenitors results in extensive skeletal defects. Using photoconversion-based cell lineage analysis, we find that sclerotome progenitors at different dorsal-ventral and anterior-posterior positions display distinct differentiation potentials. Single-cell clonal analysis combined with in vivo imaging suggests that the sclerotome mostly contains unipotent and bipotent progenitors prior to cell migration, and the fate of their daughter cells is biased by their migration paths and relative positions. Together, our work demonstrates that the sclerotome is the embryonic source of trunk fibroblasts as well as the axial skeleton, and local signals likely contribute to the diversification of distinct fibroblast subtypes.
Topics: Animals; Zebrafish; Somites; Cell Differentiation; Cell Lineage; Fibroblasts
PubMed: 36933633
DOI: 10.1016/j.ydbio.2023.03.004 -
Trends in Cell Biology Sep 2010Living organisms undergo biochemical, physiological and behavioral cycles with periods ranging from seconds to years. Cycles with intermediate periods are governed by... (Review)
Review
Living organisms undergo biochemical, physiological and behavioral cycles with periods ranging from seconds to years. Cycles with intermediate periods are governed by endogenous clocks that depend on oscillating gene expression. Here we illustrate the modalities and specific functions of post-transcriptional control of gene expression (exerted on pre-mRNAs and mRNAs) in biological clocks through two examples: the circadian clock and the vertebrate somite segmentation clock, an embryonic clock with a period far below a day. We conclude that both constitutive and cyclic post-transcriptional controls underpin clock function.
Topics: Animals; Biological Clocks; Circadian Rhythm; Embryonic Development; Gene Expression Regulation; Humans; RNA Processing, Post-Transcriptional; RNA, Messenger; Somites
PubMed: 20630760
DOI: 10.1016/j.tcb.2010.06.004 -
BMC Developmental Biology Oct 2015Components of the limb musculoskeletal system have distinct mesoderm origins. Limb skeletal muscles originate from somites, while the skeleton and attachments (tendons...
BACKGROUND
Components of the limb musculoskeletal system have distinct mesoderm origins. Limb skeletal muscles originate from somites, while the skeleton and attachments (tendons and connective tissues) derive from limb lateral plate. Despite distinct mesoderm origins, the development of muscle, skeleton and attachments is highly coordinated both spatially and temporally to ensure complete function of the musculoskeletal system. A system to study molecular interactions between somitic-derived tissues (muscles) and lateral-plate-derived tissues (skeletal components and attachments) during limb development is missing.
RESULTS
We designed a gene delivery system in chick embryos with the ultimate aim to study the interactions between the components of the musculoskeletal system during limb development. We combined the Tol2 genomic integration system with the viral T2A system and developed new vectors that lead to stable and bicistronic expression of two proteins at comparable levels in chick cells. Combined with limb somite and lateral plate electroporation techniques, two fluorescent reporter proteins were co-expressed in stoichiometric proportion in the muscle lineage (somitic-derived) or in skeleton and their attachments (lateral-plate-derived). In addition, we designed three vectors with different promoters to target muscle cells at different steps of the differentiation process.
CONCLUSION
Limb somite electroporation technique using vectors containing these different promoters allowed us to target all myogenic cells, myoblasts or differentiated muscle cells. These stable and promoter-specific vectors lead to bicistronic expression either in somitic-derived myogenic cells or lateral plate-derived cells, depending on the electroporation sites and open new avenues to study the interactions between myogenic cells and tendon or connective tissue cells during limb development.
Topics: Actins; Animals; Bone and Bones; Chick Embryo; Cyclin-Dependent Kinase Inhibitor p57; Electroporation; Extremities; Genetic Vectors; Green Fluorescent Proteins; Limb Buds; Muscle Development; Muscle, Skeletal; Myosin Light Chains; Organogenesis; Promoter Regions, Genetic; Somites
PubMed: 26518454
DOI: 10.1186/s12861-015-0088-3 -
The International Journal of... 2010Since the era of the ancient Egyptians and Greeks, the avian embryo has been a subject of intense interest to visualize the first steps of development. It has served as... (Review)
Review
Since the era of the ancient Egyptians and Greeks, the avian embryo has been a subject of intense interest to visualize the first steps of development. It has served as a pioneer model to scrutinize the question of hematopoietic development from the beginning of the 20th century. It's large size and easy accessibility have permitted the development of techniques dedicated to following the origins and fates of different cell populations. Here, we shall review how the avian model has brought major contributions to our understanding of the development of the hematopoietic system in the past four decades and how these discoveries have influenced our knowledge of mammalian hematopoietic development. The discovery of an intra-embryonic source of hematopoietic cells and the developmental link between endothelial cells and hematopoietic cells will be presented. We shall then point to the pivotal role of the somite in the construction of the aorta and hematopoietic production and demonstrate how two somitic compartments cooperate to construct the definitive aorta. We shall finish by showing how fate-mapping experiments have allowed the identification of the tissue which gives rise to the sub-aortic mesenchyme. Taken together, this review aims to give an overview of how and to what extent the avian embryo has contributed to our knowledge of developmental hematopoiesis.
Topics: Animals; Aorta; Cell Lineage; Chick Embryo; Chickens; Hematopoiesis; Hematopoietic Stem Cells; Hematopoietic System; Models, Biological; Somites
PubMed: 20711981
DOI: 10.1387/ijdb.103062tj -
The International Journal of... 2016Stromal-cell-derived factor-1 (SDF-1), the only ligand of the chemokine receptor CXCR4, is involved in skeletal muscle development. However, its role in the...
Stromal-cell-derived factor-1 (SDF-1), the only ligand of the chemokine receptor CXCR4, is involved in skeletal muscle development. However, its role in the proliferation, differentiation and migration of somite cells is not well understood. Here, we investigated its function during somite development in chicken embryos by using gain-of-function and loss-of-function experiments. Overexpression of SDF-1 was performed by electroporating SDF-1 constructs into the ventrolateral part of the somite, or by injecting SDF-1-expressing cells into the somites of stages HH14-16 chicken embryos. We found that enhanced SDF-1 signaling induced cell proliferation in the somite. This resulted in an increase in number of both myotomal and endothelial cells. In contrast, inhibition of SDF-1/CXCR4 signaling led to a reduction of myotomal cells. Injection of SDF-1 producing cells into the somite induced ectopic localization of myotomal cells in the sclerotome. Although many SDF-1-expressing somite cells colonized the limb, only a few of them developed into muscle cells. This resulted in a reduction of the limb muscle mass. This means that most myogenic progenitors were stopped on their migration towards the limb due to the high concentration of the SDF-1 signal in the somite. Most of the SDF-1-expressing somite cells found in the limb were of endothelial cell fate and they contributed to the increase in limb blood vessels. These results reveal that SDF-1 promotes the proliferation of both myogenic and angiogenic progenitor cells of the somite and controls myotome formation. Furthermore, SDF-1 controls muscle and blood vessel formation in the limb in different ways.
Topics: Animals; Avian Proteins; Blood Vessels; Body Patterning; COS Cells; Chemokine CXCL12; Chick Embryo; Chlorocebus aethiops; Extremities; Gene Expression Regulation, Developmental; Gene Transfer Techniques; Green Fluorescent Proteins; Immunohistochemistry; In Situ Hybridization; Microscopy, Fluorescence; Muscle Development; Muscle, Skeletal; Receptors, CXCR4; Signal Transduction; Somites
PubMed: 26934287
DOI: 10.1387/ijdb.150132rh -
Developmental Dynamics : An Official... Aug 2015In most vertebrates, the segmentation of the paraxial mesoderm involves the formation of metameric units called somites through a mesenchymal-epithelial transition....
BACKGROUND
In most vertebrates, the segmentation of the paraxial mesoderm involves the formation of metameric units called somites through a mesenchymal-epithelial transition. However, this process is different in Xenopus laevis because it does not form an epithelial somite. Xenopus somitogenesis is characterized by a complex cells rearrangement that requires the coordinated regulation of cell shape, adhesion, and motility. The molecular mechanisms that control these cell behaviors underlying somite formation are little known. Although the Paraxis has been implicated in the epithelialization of somite in chick and mouse, its role in Xenopus somite morphogenesis has not been determined.
RESULTS
Using a morpholino and hormone-inducible construction approaches, we showed that both gain and loss of function of paraxis affect somite elongation, rotation and alignment, causing a severe disorganization of somitic tissue. We further found that depletion or overexpression of paraxis in the somite led to the downregulation or upregulation, respectively, of cell adhesion expression markers. Finally, we demonstrated that paraxis is necessary for the proper expression of myotomal and sclerotomal differentiation markers.
CONCLUSIONS
Our results demonstrate that paraxis regulates the cell rearrangements that take place during the somitogenesis of Xenopus by regulating cell adhesion. Furthermore, paraxis is also required for somite differentiation.
Topics: Animals; Cell Adhesion; Cell Differentiation; Gene Expression Regulation, Developmental; Nuclear Proteins; Somites; Transcription Factors; Xenopus Proteins; Xenopus laevis; Zebrafish Proteins
PubMed: 26010523
DOI: 10.1002/dvdy.24294