11-P012 Left/right axis specification in the cilia mutant talpid3

Comparison between related species is a successful approach to uncover conserved and divergent principles of development. Here we studied the pattern of epithalamic asymmetry in zebrafish and medaka, two related teleost species with 115–200 million-year of independent evolution. We found that these species share a strikingly conserved overall pattern of asymmetry in the parapineal–habenular–interpeduncular system. Nodal signalling precedes the left-sided asymmetric positioning and connectivity of the parapineal organ, the enlargement of neuropil in the left habenula compared to the right habenula and the segregation of left–right habenular efferents along the dorsoventral axis of the interpeduncular nucleus. Despite the overall conservation of asymmetry, we observed heterotopic changes in the topology of parapineal efferent connectivity, heterochronic shifts in the timing of developmental events underlying the establishment of asymmetry, and divergent degrees of canalisation of embryo laterality. We are currently testing hypotheses of inter-species variation that link the topology of parapineal efferent connectivity to the underlying organisation of domains within the left habenula, and are also expanding our developmental time comparison to a broader ontogenic context. Together, these findings highlight the usefulness of zebrafish and medaka as comparative tools to study the developmental mechanisms of epithalamic asymmetry in vertebrates.