The role of Otx and Otp genes in brain development

Over the last ten years, many genes involved in the induction, specificatio n and regionalization of the brain have been identified and characterized a t the functional level through a series of animal models. Among these genes , both Otx1 and Otx2, two murine homologues of the Drosophila orthodenticle (otd) gene which encode transcription factors, play a pivotal role in the morphogenesis of the rostral brain. Classical knock-out studies have reveal ed that Otx2 is fundamental for the early specification and subsequent main tenance of the anterior neural plate. whereas Otx1 is mainly necessary for both normal corticogenesis and sense organ development. A minimal threshold of both gene products is required for correct patterning of the fore-midbr ain and positioning of the isthmic organizer. A third gene, Orthopedia (Otp ) is a key element of the genetic pathway controlling development of the ne uroendocrine hypothalamus. This review deals with a comprehensive analysis of the Otx1, Otx2 and Otp functions, and with the possible evolutionary imp lications suggested by the models in which the Otx genes are reciprocally r eplaced or substituted by the Drosophila homologue, otd.