All vertebrates share a common embryonic design based on the functional activity of homologous genes that operate during embryonic development. In recent years comparative genomics has enabled it to be shown that, in addition to coding regions, the genomic regions associated with genes involved in morphological pattern generation also contain highly conserved non-coding regions (HCNRs).  Small-scale functional studies by various groups, including ours, have demonstrated that many of these HCNRs contain cis-regulatory elements that activate gene expression in tissue specific domains during embryonic development.
 

In our group, we are initiating a genome scale study of the functional activity of the complete collection of HCNRs present in all vertebrates (approximately 3000). To that aim, we are generating stable transgenic zebrafish lines of those regions that exhibit enhancer activity. This collection, of great value to the scientific community, will be an essential tool for deciphering the molecular mechanisms and genetic networks that operate during vertebrate development.  At the same time, this collection will permit comparisons between expression patterns and enhancer sequences, which should greatly assist efforts to unravel of the language of cis-regulatory elements in the future. Moreover, functional studies of orthologous regions from different species in zebrafish will help us understand evolution. In addition, we aim to identify specific HCNRs associated with different human genetic diseases such as cancer, diabetes or deafness. Finally, we are investigating the functional relevance of specific HCNRs in an in vivo genomic context and the molecular mechanisms by which these regions function.  To this end, we are concentrating on selected HCNRs recently identified within Irx clusters.