The principal aim of this project is to determine factors that regulate the establishment of the spatially restricted pattern of expression of Hox genes in the developing vertebrate nervous system. Hox genes are true homologues of the homeotic genes first identified in Drosophila and have a central role in axial patterning in all metazoans.
Spatial enhancers will be characterised in transgenic mice using a lacZ reporter gene. Deletion and sequence analysis will determine the minimal elements required for the spatial expression of the gene under study, and this will allow us to search for candidate factors that are upstream in the regulatory cascade that leads to pattern formation in the brain. Comparison of the enhancer with similar elements from other Hox genes expressed in overlapping patterns (paralogues) and with homologous genes from other vertebrates (chick and puffer-fish) will help to determine how far these upstream regulatory networks have been conserved in evolution.