P1 Regionalisation of the brain as an evolutionarily conserved developmental mechanism.

Comparative studies of chordate neural connectivity and gene families have provided evidence for evolutionary conservation of the patterning mechanisms in brain development (review Holland & Holland, Curr. Opin. Neurobiol. 9, 1999). Based on expression patterns of ascidian and amphioxus homologues of the Otx gene and the Hox1 gene and of the ascidian Pax‐2/5/8, the chordate brain has been suggested to have tripartite development (Wada et al., Development 125, 1998; Kozmik et al., Development 126, 1999). Primitively, the chordates have regions homologous to the vertebrate forebrain, anterior midbrain and posterior hindbrain while the posterior midbrain/anterior hindbrain region seems to be a vertebrate innovation. The extent of the homologies within each of these regions between the vertebrates and their ancestors is not fully determined but the similarity of Hox gene expression patterns suggests organisational constants over evolutionary time within the posterior hindbrain region. Identification of the posterior hindbrain region as a developmental unit in vertebrates is demonstrated in the retinoid‐deficient quail. Embryos laid by quails fed a retinoid‐deficient diet have no posterior hindbrain while the anterior hindbrain is specified normally. Through DiI cell lineage tracing and a temporal analysis of gene expression characteristic of this region ( Krox‐20, Hoxb‐1, mafB, and fgf3 ), we have followed the development of this region of cells. From the initial formation of the neural plate phenotype in the retinoid‐deficient quail, there is no evidence of a posterior hindbrain. This region is never specified and all the cells of the hindbrain participate in an anterior hindbrain fate. A single retinoid injection in ovo during early development completely rescues the posterior hindbrain ensuring that the phenotype was the result of a single stimulus. Therefore cells from the posterior hindbrain respond in a coordinated regional manner to the presence or absence of a single gene inducer, retinoic acid. We present evidence of regionalisation of the vertebrate head that is up stream of segment specification. In combination with data from amphioxus and ascidians, this may represent a common mechanism for head development throughout chordate evolution. Interestingly, regional deletion with enlargement of the adjacent region is very reminiscent of the gap gene phenotype in Drosophila. It would be disregarding millions of years of divergent evolution to suggest that vitamin A is identical to a Drosophila gap gene inducer; nevertheless this data supports the hypothesis of common underlying regulation of axial regionalisation and gene hierarchies.