Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx

Background: Terminal differentiation of many cell types is controlled and m aintained by tissue- or cell-specific transcription factors. Little is know n, however, of the transcriptional networks controlled by such factors and how they regulate differentiation. The paired-type homeobox transcription f actor, Crx, has a pivotal role in the terminal differentiation of vertebrat e photoreceptors. Mutations in the human CRX gene result in either congenit al blindness or photoreceptor degeneration and targeted mutation of the mou se Crx results in failure of development of the light-detecting outer segme nt of photoreceptors. Results: We have characterized the transcriptional network controlled by Cr x by microarray analysis of gene expression in developing retinal tissue fr om Crx(+/+) and Crx(-/-) mice. These data were combined with analyses of ge ne expression in developing and adult retina, as well as adult brain. The m ost abundant elements of this network are ten photoreceptor-specific or -en riched genes, including six phototransduction genes. All of the available 5 ' regulatory regions of the putative Crx targets contain a novel motif that is composed of a head-to-tail arrangement of two Crx-binding-element-like sequences. Analysis of the 5' regions of a set of mouse and human genes sug gests that this motif is specific to Crx targets. Conclusions: This study demonstrates that cDNA microarrays can be successfu lly used to define the transcriptional networks controlled by transcription factors in vertebrate tissue in vivo.