Genetic and molecular roles of Otx homeodomain proteins in head development

Insights into the molecular mechanisms underlying neural development in vertebrates come from the cloning and the functional analysis of genes which are involved in the molecular pathways leading to neural induction, tissue specification and regionalization of the brain. Among them, transcription factors belonging to the orthodenticle family (Otx1, Otx2) play an important role during early and later events required for proper brain development. To better understand their functions, several mouse mutants have been generated by homologous recombination. Their analysis clearly indicates that Otx1 is involved in corticogenesis, sense organ development and pituitary functions, while Otx2 is necessary earlier in development, for the correct anterior neural plate specification and organisation of the primitive streak. A molecular mechanism depending on a precise threshold of OTX proteins is necessary for the correct positioning of the isthmic region and for anterior brain patterning. Finally, vertebrate Otx genes share functional equivalence with the Drosophila homologue otd, indicating that the genetic mechanisms underlying pattern formation in insect and mammalian brain development are evolutionarily conserved.