Key Points
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During somitogenesis, presomitic mesoderm (PSM) can be divided into at least two distinct regions: region I (posterior PSM) and region II (anterior PSM), which correspond to the two distinct cellular states, state I and state II.
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No signs of segment specification can be detected at a molecular or cellular level in region I, but PSM cells acquire rostrocaudal polarity and become competent to segment once they have reached region II.
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Cyclical gene expression that reflects an underlying segmentation clock is translated into Notch activity that keeps the oscillations of neighbouring PSM cells synchronized in region I.
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Expression of delta-like 1 (Dll1) in region II, which is regulated by mesoderm posterior 2 (Mesp2) through the Notch signalling pathway, determines the rostrocaudal polarity of somites.
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Notch signalling can be either presenilin 1 (Psen1) dependent or independent; the former is involved in inducing Dll1 expression and the latter in inhibiting Dll1 expression. Mesp2 might stimulate the inhibitory pathway and suppress the induction pathway.
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The transition from state I to state II is controlled by the level of fibroblast growth factor (Fgf) signalling. A high level of Fgf activation in the posterior PSM maintains PSM cells in an immature state, whereas low Fgf levels accelerate the maturation process of PSM cells in the anterior PSM.
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Because the Fgf activation domain retreats as somitogenesis proceeds, the wavefront, which is the interphase between region I and region II, gradually moves back. So, periodic interactions between the wavefront and the oscillation wave create a regularly spaced somite border.
Abstract
The reiterated structures of the vertebrate axial skeleton, spinal nervous system and body muscle are based on the metameric structure of somites, which are formed in a dynamic morphogenetic process. Somite segmentation requires the activity of a biochemical oscillator known as the somite-segmentation clock. Although the molecular identity of the clock remains unknown, genetic and experimental evidence has accumulated that indicates how the periodicity of somite formation is generated, how the positions of segment borders are determined, and how the rostrocaudal polarity within somite primordia is generated.
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DATABASES
Glossary
- PARAXIAL MESODERM
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A subpopulation of mesoderm that lies on both sides of the neural tube, which gives rise to somites.
- CEPHALOCHORDATE
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A subphylum of chordates that includes the amphioxus Branchiostoma, which has a notochord, dorsal nervous system and segmented trunk, but lacks characters such as complex paired sensory organs and a true brain.
- PRESOMITIC MESODERM
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Precursor unsegmented mesoderm, which generates somites on segmentation.
- CYCLING GENE
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A gene, the expression of which oscillates rostrocaudally in the presomitic mesoderm.
- ROSTROCAUDAL POLARITY
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The difference between the rostral (anterior) and caudal (posterior) halves of a somite that underlies a difference in future developmental fates.
- SEGMENT-POLARITY GENE
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A gene originally identified in Drosophila early development, the expression of which divides the embryo into units that are 14 segments wide.
- SCLEROTOME
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Mesenchymal cell mass located in the medial region of a somite, from which the axial skeleton derives
- PRIMITIVE STREAK
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A longitudinal cleft formed on the surface of the amniote early embryo by a convergence of cells. At the onset of gastrulation, epiblast cells migrate towards and into the streak, and in so doing acquire mesodermal cell fate.
- TAILBUD
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The caudal end of the tail region at which gastrulation continues to generate precursors for the paraxial mesoderm and the neural tube.
- EPITHELIAL SOMITE
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Spherical epithelial structure made up of epithelial cells that differentiate from mesenchymal cells on segmentation.
- AMNIOTE
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Animal, such as reptile, bird or mammal, whose eggs contain an amnion — a membrane that surrounds the embryo and helps retain fluids.
- SURFACE ECTODERM
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The outermost germ layer of the embryo that develops during gastrulation. Also the cell layer that covers the paraxial mesoderm, from which several diffusible factors are secreted that induce somitic cells to take on the dermomyotome fate.
- DERMOMYOTOME
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Epithelial cell layer in the dorsolateral region of the somite that faces the ectoderm and further differentiates into the most dorsal dermatome, which later differentiates into dermis and myotome — future skeletal muscles.
- NEURONAL HYPERPLASIA
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Excessive formation of neuronal tissues due to transdifferentiation as a result of defects in Notch signalling.
- HOMOTYPIC INTERACTION
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Protein interaction between molecules of the same type.
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Saga, Y., Takeda, H. The making of the somite: molecular events in vertebrate segmentation. Nat Rev Genet 2, 835–845 (2001). https://doi.org/10.1038/35098552
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DOI: https://doi.org/10.1038/35098552
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