Partners and International Organizations
(English)
|
University of Freiburg i. Br. (D), University of Murcia (E), Fondazione Centro San Raftaele del Mone Tabor (I), Biocenter (CH), Max Planck Institute of Biophysical Chemistry (D), Institut
d'Embryologie Cellulaire et Moléculaire du CNRS (F), University of Mainz (D)
|
Abstract
(English)
|
In the course of this grant we have carried out investigations on the genetic mechanisms that control embryonic brain development, and have demonstrated that surprising similarities exist in the underlying molecular programs in insects and vertebrates. Indeed, homologous regulatory genes have been indentified which control regionalization, pattern generation and cellular identity in a similar manner in both animal phyla. Among these genes are the Hox genes and the otd/Otx family, as well as gene groups belonging to the Pax 2,5,8 gene family, the ey/Pax6 gene family and the ems/Emx gene family. For all of these cases we have been able to show that the fly gene homologs are expressed in the embryonic fly brain in a manner which is remarkable similar to that of the expression of the homologous vertebrate genes in the embryonic vertebrate brain. Moreover, we have been able to show that this similarity is extends beyond expression to the level of gene function as determined by genetic loss-of-function and gain-of-function experiments.
Taken together, these investigations demonstrate that the genetic programe which direct embryonic brain development are remarkably conserved and lend further support to our hypothesis that a common molecular Bauplan underlies brain development in insects and vertebrates. In consequence, it seems increasingly likely that both modern brain types share their evolutionary origin in an common ancestral brain which was established before the protostome-deuterostome divergence over 600 million ago.
To gain further comprehensive insight into the evolutionary conservation of molecular control networks that direct embryonic brain development in insects and vertebrates, we have combined specific in vivo genetic manipulations in Drosophila with the use of high-density oligonucleotide arrays (gene chips) to identify the comprehensive set of downstream genes. Our results on the otd cephalic gap gene and on the lab homeotic gene have already led to the identification of several hundred downstream genes, which encode well known transcription factors, signalling molecules, cell cycle control elements, proteases, transmembrane proteins, structural proteins and enzymes. With the remarkable and extensive set of results already obtained by this functional genomic approach, we have now set the stage for a revolutionary complete genomic analsis of molecular expression profiles in normal and genetically manipulate embryonic brains.
|
