Otx genes and the genetic control of brain morphogenesis

Understanding the genetic mechanisms that control brain patterning in verte brates represents a major challenge for developmental neurobiology. The clo ning of genes likely to be involved in the organization of the brain and an analysis of their roles have revealed insights into the molecular pathways leading to neural induction, tissue specification, and regionalization of the brain. Among these genes, both Otx1 and Otx2, two murine homologs of th e Drosophila orthodenticle (otd) gene, contribute to several steps in brain morphogenesis. Recent findings have demonstrated that Otx2 plays a major r ole in gastrulation and in the early specification of the anterior neural p late while Otx1 is mainly involved in corticogenesis, and Otx1 and Otx2 gen es cooperate in such a way that a minimal level of OTX proteins are require d for proper regionalization and subsequent patterning of the developing br ain. Finally, experiments have shown functional equivalence between Drosoph ila otd and vertebrate Otx genes, suggesting a surprising conservation of f unction required in brain development throughout evolution.