The clock and wavefront model is a model used to describe the process of

somitogenesis Somitogenesis is the process by which somites form. Somites are bilaterally paired blocks of paraxial mesoderm that form along the anterior-posterior axis of the developing embryo in segmented animals. In vertebrates, somites give rise to skelet ...

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...

s. Somitogenesis is the process by which

somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide ...

s, blocks of

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Emb ...

that give rise to a variety of connective tissues, are formed. The model describes the splitting off of somites from the paraxial mesoderm as the result of oscillating expression of particular

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s and their gradients.

Overview

Once the cells of the pre-somitic mesoderm are in place following by cell migration during gastrulation, oscillatory expression of many genes begins in these cells as if regulated by a developmental "clock." This has led many to conclude that somitogenesis is coordinated by a "clock and wave" mechanism. More technically, this means that somitogenesis occurs due to the largely cell-autonomous oscillations of a network of genes and gene products which causes cells to oscillate between a permissive and a non-permissive state in a consistently timed-fashion, like a clock. These genes include members of the FGF family, Wnt and Notch pathway, as well as targets of these pathways. The wavefront 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 of the more anterior pre-somitic mesoderm, forming a somite boundary and resetting the process for the next somite. In particular, the cyclic activation of the Notch pathway appears to be of great importance in the wavefront-clock model. It has been suggested that the activation of Notch cyclically activates a

cascade Cascade, Cascades or Cascading may refer to: Science and technology Science *Cascade waterfalls, or series of waterfalls * Cascade, the CRISPR-associated complex for antiviral defense (a protein complex) * Cascade (grape), a type of fruit * Bioc ...

of genes necessary for the somites to separate from the main paraxial body. This is controlled by different means in different species, such as through a simple

negative feedback Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...

loop in zebrafish or in a complicated process in which FGF and Wnt clocks affect the Notch clock, as in chicks and mice. Generally speaking, however, the segmentation clock model is highly evolutionarily conserved. 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 The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ca ...

, 90 minutes in chicks, and 100 minutes in snakes.

Autonomy of oscillation

Gene oscillation in presomitic cells is largely, but 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, some cellular inter-dependency has been displayed in studies concerning the protein

Sonic hedgehog Sonic hedgehog protein (SHH) is encoded for by the ''SHH'' gene. The protein is named after the character ''Sonic the Hedgehog''. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organogenesis a ...

(Shh) in somitogenesis. Although expression of Shh pathway proteins has not been reported to oscillate in the pre-somitic mesoderm, they are expressed within the pre-somitic mesoderm during somitogenesis. When the notochord is ablated during somitogenesis in the chick embryo, the proper number of somites forms, but the segmentation clock is delayed for the posterior two thirds of the somites. The anterior somites are not affected. In one study, this phenotype was mimicked by 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.

Overview

Autonomy of oscillation

See also

References

Further reading