Figure 1.

The vertebrate segmentation clock oscillator.

(a) Schematic showing the dorsal view of a 2 day-old chicken embryo, and the position of somites and the PSM that flank the axial neural tube. As somites bud off the anterior end of the PSM, new cells are recruited into the posterior PSM from the progenitor cells in the tail bud [4–6]. (b) The PSM tissue in a is magnified in b to illustrate the evidence for an oscillator underlying vertebrate segmentation. Periodic waves of transcriptional expression of the cHairy1 gene (successive waves shown in different colours) across the PSM share the same periodicity as somite formation, 90 minutes in chick [19]. The red box is magnified at the bottom of this figure to illustrate what this process means at the level of individual PSM cells. During each oscillation, individual cells within the PSM turn on and off the gene. This dynamic expression at the level of single cells, by virtue of being synchronised across the PSM, results in apparent ‘waves’ of gene expression that ‘move’ across the PSM (top part of panel). The cells themselves suffer very little anterior movement at all. However, as somites bud off the rostral PSM and new cells enter the caudal PSM, individual cells within the PSM become progressively more anteriorly displaced in the PSM (see the red box in the top part of the panel). (c) A schematic diagram integrating the domains of various signalling activities in the PSM – the wavefront of determination on the left hand side, and the clock on the right. The system of opposing gradients of Fgf (green), Wnt (blue) and retinoic acid (RA - purple) signalling in the PSM positions the determination front (red) along the PSM [18]. The determination front marks the position where the next prospective boundary will form, thereby defining somite size [18]. As these cells mature, the anterior (A) and posterior (P) somite compartments become specified. In the most rostral PSM the definitive morphological boundary of the next prospective somite forms. As indicated on the right side of the diagram, within this same PSM tissue, waves of Notch, Fgf, and Wnt cyclic gene expression controlled by the segmentation clock oscillator traverse the PSM periodically (black spiral symbol). The oscillations slow down as they reach the rostral PSM. Wnt activity appears to act as (part of) the pacemaker mechanism to regulate the periodicity of cyclic gene oscillations [59]. Prospective somites in the PSM are numbered with somite S0 being the forming somite and the somites next to form labelled in negative Roman numerals, S-I etc[90]. Segmented somites are numbered in positive Roman numerals, with SI being the most recently formed somite.