Otx genes in the development and evolution of the vertebrate brain

Most of the gene candidates for the control of developmental programmes tha t underlie brain morphogenesis in vertebrates are the orthologues of Drosop hila genes coding for signalling molecules or transcription factors. Among these, the orthodenticle group. including the Drosophila orthodenticle (otd ) and the vertebrate Otx1 and Otx2 genes, is mostly involved in fundamental processes of anterior neural patterning. In mouse, Drosophila and intermed iate species otd/Otx genes have shown a remarkable similarity in expression pattern suggesting that they could be part of a conserved control system o perating in the brain and different from that coded by the HOX complexes co ntrolling the hindbrain and spinal cord. In order to verify this hypothesis , a series of mouse models have been generated in which the functions of th e murine Otx genes were: (i) fully inactivated, (ii) replaced with each oth er, and (iii) replaced with the Drosophila otd gene. The data obtained high light a crucial role for the Otx genes in specification, regionalization an d terminal differentiation of rostral central nervous system and lead to hy pothesize that modification of their regulatory control may have influenced the morphogenesis and evolution of the brain. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.