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 vertebrates. The somites give rise to skeletal muscle, cartila ...

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

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somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along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

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 ...

that give rise to a variety of connective tissues, are formed. The model describes the splitting off of somites from the

paraxial mesoderm Paraxial mesoderm, also known as presomitic or somitic mesoderm, is the area of mesoderm in the neurulating embryo that flanks and forms simultaneously with the neural tube. The cells of this region give rise to somites, blocks of tissue running ...

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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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, or Cascading may refer to: Science and technology Science * Air shower (physics), a cascade (particle shower) of subatomic particles and ionized nuclei ** Particle shower, a cascade of secondary particles produced as the result of a high ...

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 (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...

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, 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 species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...

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

Oscillation autonomy

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 a major signaling molecule of embryonic development in humans and animals, encoded by the ''SHH'' gene. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organoge ...

(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

Oscillation autonomy

See also

References

Further reading