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Current Opinion in Genetics &... Jun 2015England's King Richard III, whose skeleton was recently discovered lying ignobly beneath a parking lot, suffered from a lateral curvature of his spinal column called... (Review)
Review
England's King Richard III, whose skeleton was recently discovered lying ignobly beneath a parking lot, suffered from a lateral curvature of his spinal column called scoliosis. We now know that his scoliosis was not caused by 'imbalanced bodily humors', rather vertebral defects arise from defects in embryonic elongation and segmentation. This review highlights recent advances in our understanding of post-gastrulation biomechanics of the posteriorly advancing tailbud and somite morphogenesis. These processes are beginning to be deciphered from the level of gene networks to a cross-scale physical model incorporating cellular mechanics, the extracellular matrix, and tissue fluidity.
Topics: Animals; Body Patterning; Cell Movement; Cell Proliferation; Extracellular Matrix; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Models, Biological; Morphogenesis; Notochord; Somites; Vertebrates
PubMed: 25796079
DOI: 10.1016/j.gde.2015.02.005 -
Developmental Dynamics : An Official... Jun 2007The regular pattern of somite segmentation depends on a clock, the somite segmentation clock, in the form of a gene expression oscillator, operating in the presomitic... (Review)
Review
The regular pattern of somite segmentation depends on a clock, the somite segmentation clock, in the form of a gene expression oscillator, operating in the presomitic mesoderm (the PSM) at the tail end of the vertebrate embryo. Genetic screens and other approaches have identified a variety of genes, including components and targets of the Notch signalling pathway, that show transcriptional oscillations in this region and appear to be necessary for correct segmentation. Mathematical modelling shows that the oscillations could plausibly be generated by a simple mechanism of delayed negative feedback, based on autoinhibition of Notch target genes of the Hes/her family by their own protein products. To move beyond plausible models to an experimentally validated theory, however, it is necessary to measure the parameters on which the proposed model is based and to devise ways of probing the dynamics of the system by means of timed disturbances so as to compare with the model's predictions. Some progress is being made in these directions.
Topics: Animals; Biological Clocks; Body Patterning; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mutation; Somites
PubMed: 17436283
DOI: 10.1002/dvdy.21154 -
Journal of Anatomy 2001Vertebrate somitogenesis has been shown to be associated with a molecular oscillator, the segmentation clock, whose periodicity matches that of the process of... (Review)
Review
Vertebrate somitogenesis has been shown to be associated with a molecular oscillator, the segmentation clock, whose periodicity matches that of the process of somitogenesis. The existence of such a clock in presomitic mesoderm (PSM) cells was originally proposed in theoretical models such as the 'clock and wavefront'. Molecular evidence for the existence of this clock in vertebrates has been obtained on the basis of the periodic expression of several genes, most of which are related to the Notch signalling pathway. These genes are expressed in a dynamic sequence which appears as a wave sweeping caudo-rostrally along the whole PSM once during each somite formation. Notch-pathway mouse and fish mutants lose the dynamic expression of the cycling genes, indicating that Notch signalling is required for their periodic expression, or is required to coordinate the oscillations between PSM cells. Therefore Notch signalling is either part of the mechanism of the oscillator itself or acts as a cofactor required for cycling gene expression. A further potentially important role for the segmentation clock is to periodically activate Notch signalling in the rostral presomitic mesoderm, thereby generating the periodic formation of somite boundaries.
Topics: Animals; Chick Embryo; Embryonic Induction; Gene Expression; Membrane Proteins; Mesoderm; Morphogenesis; Receptors, Notch; Somites; Vertebrates
PubMed: 11523819
DOI: 10.1046/j.1469-7580.2001.19910169.x -
Developmental Biology Oct 2022The head-tail axis in birds and mammals develops from a growth zone in the tail-end, which contains the node. This growth zone then forms the tailbud. Labelling...
The head-tail axis in birds and mammals develops from a growth zone in the tail-end, which contains the node. This growth zone then forms the tailbud. Labelling experiments have shown that while many cells leave the node and tailbud to contribute to axial (notochord, floorplate) and paraxial (somite) structures, some cells remain resident in the node and tailbud. Could these cells be resident axial stem cells? If so, do the node and tailbud represent an instructive stem cell niche that specifies and maintains these stem cells? Serial transplantation and single cell labelling studies support the existence of self-renewing stem cells and heterotopic transplantations suggest that the node can instruct such self-renewing behaviour. However, only single cell manipulations can reveal whether self-renewing behaviour occurs at the level of a cell population (asymmetric or symmetric cell divisions) or at the level of single cells (asymmetric divisions only). We combine data on resident cells in the node and tailbud and review it in the context of axial development in chick and mouse, summarising our current understanding of axial stem cells and their niche and highlighting future directions of interest.
Topics: Animals; Cell Division; Mammals; Mesoderm; Mice; Notochord; Somites; Stem Cells
PubMed: 35779606
DOI: 10.1016/j.ydbio.2022.06.015 -
International Journal of Molecular... Mar 2018The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes....
The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated.
Topics: ADAMTS5 Protein; Animals; Cell Differentiation; Embryo, Nonmammalian; Extracellular Space; Gene Expression Regulation, Developmental; Gene Silencing; Hedgehog Proteins; Morphogenesis; Muscle Development; Signal Transduction; Somites; Zebrafish
PubMed: 29518972
DOI: 10.3390/ijms19030766 -
ELife Feb 2022Angioblasts that form the major axial blood vessels of the dorsal aorta and cardinal vein migrate toward the embryonic midline from distant lateral positions. Little is...
Angioblasts that form the major axial blood vessels of the dorsal aorta and cardinal vein migrate toward the embryonic midline from distant lateral positions. Little is known about what controls the precise timing of angioblast migration and their final destination at the midline. Using zebrafish, we found that midline angioblast migration requires neighboring tissue rearrangements generated by somite morphogenesis. The somitic shape changes cause the adjacent notochord to separate from the underlying endoderm, creating a ventral midline cavity that provides a physical space for the angioblasts to migrate into. The anterior to posterior progression of midline angioblast migration is facilitated by retinoic acid-induced anterior to posterior somite maturation and the subsequent progressive opening of the ventral midline cavity. Our work demonstrates a critical role for somite morphogenesis in organizing surrounding tissues to facilitate notochord positioning and angioblast migration, which is ultimately responsible for creating a functional cardiovascular system.
Topics: Animals; Animals, Genetically Modified; Embryo, Nonmammalian; Embryonic Development; Gene Expression Regulation, Developmental; Neovascularization, Physiologic; Retinoids; Somites; Tretinoin; Zebrafish; Zebrafish Proteins; p-Aminoazobenzene
PubMed: 35137687
DOI: 10.7554/eLife.74821 -
The FEBS Journal Apr 2016During embryonic development, formation of individual vertebrae requires that the paraxial mesoderm becomes divided into regular segmental units known as somites.... (Review)
Review
During embryonic development, formation of individual vertebrae requires that the paraxial mesoderm becomes divided into regular segmental units known as somites. Somites are sequentially formed at the anterior end of the presomitic mesoderm (PSM) resulting from functional interactions between the oscillatory activity of signals promoting segmentation and a moving wavefront of tissue competence to those signals, eventually generating a constant flow of new somites at regular intervals. According to the current model for somitogenesis, the wavefront results from the combined activity of two opposing functional gradients in the PSM involving the Fgf, Wnt and retinoic acid (RA) signaling pathways. Here, I use published data to evaluate the wavefront model. A critical analysis of those studies seems to support a role for Wnt signaling, but raise doubts regarding the extent to which Fgf and RA signaling contribute to this process.
Topics: Animals; Humans; Mesoderm; Morphogenesis; Signal Transduction; Somites
PubMed: 26662366
DOI: 10.1111/febs.13622 -
Developmental Dynamics : An Official... Jun 2007Elaborate somite patterning is based upon dynamic gene regulation within the presomitic mesoderm (PSM), which is derived from the primitive streak and tail bud in the... (Review)
Review
Elaborate somite patterning is based upon dynamic gene regulation within the presomitic mesoderm (PSM), which is derived from the primitive streak and tail bud in the later stage mouse embryo. The Notch signaling pathway and its regulators are major components of most of the events required for temporally and spatially coordinated somite formation. The PSM can be subdivided into at least two domains, based upon transcriptional regulation and gene function. In the posterior PSM, the basic helix-loop-helix (bHLH) protein Hes7 plays a central role in generating a traveling wave of gene expression by negatively regulating the transcription of its target genes. This in turn may define the somite spacing and future segmental units. In the anterior PSM, cells begin to form segmental patterning by acquiring rostral or caudal identities of somite primordia and by defining the segmental border, which must be coupled with the segmentation clock. The link between the clock and segmental border formation is of fundamental importance during somitogenesis. During this process, Mesp2, another basic HLH protein, plays a critical role in the anterior PSM. In this review, I further clarify the dynamic processes leading to segmental border formation in the developing mouse embryo.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Body Patterning; Down-Regulation; Gene Expression Regulation, Developmental; Receptors, Notch; Somites
PubMed: 17394251
DOI: 10.1002/dvdy.21143 -
Seminars in Cell & Developmental Biology Oct 2014Heterochrony, or a change in developmental timing, is an important mechanism of evolutionary change. Historically the concept of heterochrony has focused alternatively... (Review)
Review
Heterochrony, or a change in developmental timing, is an important mechanism of evolutionary change. Historically the concept of heterochrony has focused alternatively on changes in size and shape or changes in developmental sequence, but most have focused on the pattern of change. Few studies have examined changes in the mechanisms that embryos use to actually measure time during development. Recently, evolutionary studies focused on changes in distinct timekeeping mechanisms have appeared, and this review examines two such case studies: the evolution of increased segment number in snakes and the extreme rostral to caudal gradient of developmental maturation in marsupials. In both examples, heterochronic modifications of the somite clock have been important drivers of evolutionary change.
Topics: Animals; Biological Evolution; Gene Expression Regulation, Developmental; Humans; Morphogenesis; Somites
PubMed: 24994599
DOI: 10.1016/j.semcdb.2014.06.015 -
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