The making of the somite: molecular events in vertebrate segmentation

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Abstract
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. 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. 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. 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. 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. 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. 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.