Time, space and the vertebrate body axis.

Anterior-posterior (A-P) patterning of the vertebrate main body axis regulated by timing. Anterior structures are specified early, posterior late. (1) Timing involves timed decision points as emphasised by the Wnt studies of Sokol and colleagues. It also involves complex timers, where large parts of the axis are patterned sequentially by a common upstream mechanism (articles by Durston et al., Mullins et al., Oates et al.,). (2) A gastrula BMP-anti BMP dependent time-space translation (TST) mechanism was demonstrated for the trunk section of the axis (Durston). (3) Thisses' studies emphasise the importance of BMP-anti BMP and the organiser inducing factor nodal for A-P patterning. (4) Meinhardt's interesting studies on the organiser and A-P patterning are reviewed in relation to TST. (5) Mullins' investigations show that anti-BMP dependent TST starts earlier (at the blastula stage) and extends further anteriorly (to the anterior head). Sive's studies imply it may extend further still to the "extreme anterior domain" (EAD). (6) The somitogenesis timer (clock) is presented. Stern's and Oates' findings are discussed. (7) Relations between somitogenesis and axial TST are discussed. (8) Relations of classical axial patterning pathways to TST decision points and somitogenesis are inventarised. In conclusion, all of these findings point to an integral BMP-anti BMP dependent A-P TST mechanism, running from cement gland in the EAD, Six3 and the anterior tip of the forebrain at blastula stages to Hox13 and the tip of the tail by the mid neurula stage. TST acts via sequential timed transitions between ventral (unstable, timed) and dorsal (stabilised) states. In the trunk-tail, the timer is thought to be Hox temporal collinearity and TST depends on Hox function. In the head, TST is under investigation. The somitogenesis clock is upstream of the TST timer, providing precision in the posterior part of the axis at least. Classical A-P signalling pathways: retinoids, FGFs and Wnts, change behaviour at functional decision points on the axis.