FUNCTIONAL CONSERVATION OF VERTEBRATE 7-UP RELATED GENES IN NEUROGENESIS AND EYE DEVELOPMENT

Several members of the steroid receptor superfamily, including the transcription factor COUP, are closely related to the Drosophila gene seven-up (svp) which is required for the development of the embryonic central nervous system (CNS) and specific photoreceptor cells of the eye. We have identified and characterized two zebrafish (Brachydanio rerio) members of this subfamily of orphan nuclear receptors. While one of them (svp[44]) is the zebrafish cognate of COUP, the second (svp[46]) seems to be a novel member of the COUP/svp group. The proteins encoded by both genes contain highly conserved DNA-binding and putative ligand-binding domains, indicating close similarities in target sequence recognition and ligand binding. Analysis of the spatial distribution of their transcripts in whole-mount embryos revealed that the CNS is a major site of expression for both genes. At early embryonic stages, both genes are expressed in domains corresponding to specific rhombomere primordia in the hindbrain. This suggests an involvement in hindbrain segmentation and/or rhombomere specification. Moreover, transcripts derived from both genes are detected within distinct areas of the eye rudiments, suggesting roles in eye patterning and/or cell differentiation. In the case of the svp[44] gene, expression is also observed within specific parts of the midbrain, diencephalon and telencephalon. These results represent the first evidence that at least some of the nervous system and eye-specific functions of Drosophila svp are conserved in vertebrates.