Pinealocytes and photoreceptors of the retina originate from a common ancestral cell type and are able to secrete the hormone melatonin. Homeobox genes encode transcription factors with a DNA-binding homeodomain and are known to switch on a cascade of genes important for organogenesis. Members of the orthodenticle homeobox gene family play a fundamental role in development of photoreceptors and rostral brain regions; among these, the retinal cone-rod homeobox gene (Crx) is involved in regulation of genes in retinal photoreceptors and pinealocytes, whereas the Otx2 gene is essential for general embryonic brain development.

We have investigated the expression of Crx and Otx2 in the rat retina and the brain with focus on the pineal gland. Crx and Otx2 mRNAs were detected by northern blots and in situ hybridization. The proteins were detected by western blots and immunohistochemistry. Further, the ontogenetic expression patterns of Crx and Otx2 were investigated from embryonic day sixteen (E16) to postnatal day thirty (P30).

Our results revealed that Crx and Otx2 are strongly expressed in both the retina and pineal gland. During ontogenesis, Otx2 is expressed earlier than Crx. These results support the hypothesis that the pinealocyte and retinal photoreceptor share a common ancestral cell.The data further indicate that Otx2 and Crx are required in the pineal gland and retina for both cell fate determination and to maintain phenotype, by controlling the expression of the set of phototransduction/melatonin synthesis genes that are expressed at significant levels exclusively in these tissues.