Somitogenesis
Encyclopedia
Somitogenesis is the process by which somites are produced. Somites are bilaterally paired blocks of mesoderm
that form along the anterior-posterior axis of the developing embryos of segmented animals, often originating in an anterior to posterior direction. In vertebrates, somites give rise to skeletal muscles, trunk skeleton and dermis, and form from presomitic mesoderm (PSM). Different organisms have different numbers of somites, for example frogs have ~10, humans have 33, fish have ~48, and snakes have more than 300.
Somitogenesis is an active area of investigation in many laboratories.
The PSM region from which somites arise in vertebrates is also called paraxial mesoderm because of its position flanking the notochord and extending along the anterior-posterior axis of the developing organism. Fate mapping
experiments at the blastula
stage show PSM progenitors at the marginal zone/primitive streak
(depending on the organism), in regions flanking the organizer. Transplant experiments show that only at the late gastrula stage are these cells committed to PSM, meaning that fate determination is tightly controlled by local signals and is not predetermined. For instance, exposure of PSM to Bone Morphogenetic Protein
s (BMPs) ventralizes the tissue, however in vivo, BMP antagonists secreted by the organizer (such as noggin and chordin) prevent this and thus promote the formation of dorsal structures.
Once PSM cells have been placed by cell migration during gastrulation, oscillatory expression of many genes begins in these cells as if a developmental clock has been set. These genes include members of the FGF
family, Wnt
and Notch
pathway, as well as targets of these pathways. Somitogenesis is thought to occur via a “clock and wavefront” model, in which largely cell autonomous oscillations in a network of genes and gene products causes cells to oscillate between a permissive and a non-permissive state in a consistently timed fashion like a clock. The wavefront consists of opposing Wnt/FGF and retinoic acid gradients which progresses slowly in an anterior to posterior direction. As the wavefront of signaling comes in contact with cells in the permissive state, they undergo a mesenchymal-epithelial transition
and pinch off from the more posterior PSM, forming a somite boundary, resetting the process for the next somite. Intrinsic expression of “clock genes” must oscillate with a periodicity equal to the time necessary for one somite to form, for example 30 minutes in zebrafish, 90 minutes in chicks, 100 minutes in snakes.
Gene oscillation in presomitic cells is not completely cell autonomous. When Notch signaling is disrupted in zebrafish, neighboring cells no longer oscillate synchronously, indicating that Notch signaling is important for keeping neighboring populations of cells synchronous. In addition, when the notochord is ablated during somitogenesis in the chick embryo, the proper number of somites form, but the segmentation clock is delayed for the posterior two thirds of the somites. The anterior somites are not affected. This phenotype was mimicked by addition of Sonic hedgehog
(Shh) inhibitors, and timely somite formation was rescued by exogenous Shh protein, showing that the missing signal produced by the notochord is mediated by Shh. Although expression of Shh pathway proteins has not been reported to oscillate in the PSM, they are expressed within the PSM during somitogenesis.
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
that form along the anterior-posterior axis of the developing embryos of segmented animals, often originating in an anterior to posterior direction. In vertebrates, somites give rise to skeletal muscles, trunk skeleton and dermis, and form from presomitic mesoderm (PSM). Different organisms have different numbers of somites, for example frogs have ~10, humans have 33, fish have ~48, and snakes have more than 300.
Somitogenesis is an active area of investigation in many laboratories.
The PSM region from which somites arise in vertebrates is also called paraxial mesoderm because of its position flanking the notochord and extending along the anterior-posterior axis of the developing organism. Fate mapping
Fate mapping
Introduction=Fate mapping is a method of understanding the embryonic origin of various tissues in the adult organism by establishing the correspondence between individual cells or groups of cells at one stage of development and their progeny at later stages of development...
experiments at the blastula
Blastula
The blastula is a hollow sphere of cells formed during an early stage of embryonic development in animals . The blastula is created when the zygote undergoes the cell division process known as cleavage. The blastula is preceded by the morula and is followed by the gastrula in the developmental...
stage show PSM progenitors at the marginal zone/primitive streak
Primitive streak
The primitive streak is a structure that forms during the early stages of avian, reptilian and mammalian embryonic development.-Introduction:...
(depending on the organism), in regions flanking the organizer. Transplant experiments show that only at the late gastrula stage are these cells committed to PSM, meaning that fate determination is tightly controlled by local signals and is not predetermined. For instance, exposure of PSM to Bone Morphogenetic Protein
Bone morphogenetic protein
Bone morphogenetic proteins are a group of growth factors also known as cytokines and as metabologens . Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue...
s (BMPs) ventralizes the tissue, however in vivo, BMP antagonists secreted by the organizer (such as noggin and chordin) prevent this and thus promote the formation of dorsal structures.
Once PSM cells have been placed by cell migration during gastrulation, oscillatory expression of many genes begins in these cells as if a developmental clock has been set. These genes include members of the FGF
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
family, Wnt
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
and Notch
Notch signaling
The notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms.Notch is present in all metazoans, and mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass...
pathway, as well as targets of these pathways. Somitogenesis is thought to occur via a “clock and wavefront” model, in which largely cell autonomous oscillations in a network of genes and gene products causes cells to oscillate between a permissive and a non-permissive state in a consistently timed fashion like a clock. The wavefront consists of opposing Wnt/FGF and retinoic acid gradients which progresses slowly in an anterior to posterior direction. As the wavefront of signaling comes in contact with cells in the permissive state, they undergo a mesenchymal-epithelial transition
Mesenchymal-epithelial transition
A mesenchymal-epithelial transition is a reversible biological process that involves the transition from motile, multipolar or spindle-shaped mesenchymal cells to planar arrays of polarized cells called epithelia. MET is the reverse process of epithelial-mesenchymal transition...
and pinch off from the more posterior PSM, forming a somite boundary, resetting the process for the next somite. Intrinsic expression of “clock genes” must oscillate with a periodicity equal to the time necessary for one somite to form, for example 30 minutes in zebrafish, 90 minutes in chicks, 100 minutes in snakes.
Gene oscillation in presomitic cells is not completely cell autonomous. When Notch signaling is disrupted in zebrafish, neighboring cells no longer oscillate synchronously, indicating that Notch signaling is important for keeping neighboring populations of cells synchronous. In addition, when the notochord is ablated during somitogenesis in the chick embryo, the proper number of somites form, but the segmentation clock is delayed for the posterior two thirds of the somites. The anterior somites are not affected. This phenotype was mimicked by addition of Sonic hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
(Shh) inhibitors, and timely somite formation was rescued by exogenous Shh protein, showing that the missing signal produced by the notochord is mediated by Shh. Although expression of Shh pathway proteins has not been reported to oscillate in the PSM, they are expressed within the PSM during somitogenesis.