IMPLICATION OF OTX2 IN PIGMENT-EPITHELIUM DETERMINATION AND NEURAL RETINA DIFFERENTIATION

The expression pattern of Otx2, a homeobox-containing gene, was analyz ed from the beginning of eye morphogenesis until neural retina differe ntiation in chick embryos. Early on, Otx2 expression was diffuse throu ghout the optic vesicles but became restricted to their dorsal part wh en the vesicles contacted the surface ectoderm. As the optic cup forms , Otx2 was expressed only in the outer layer, which gives rise to the pigment epithelium. This early Otx2 expression pattern was complementa ry to that of PAX2, which localizes to the ventral half of the develop ing eye and optic stalk. Otx2 expression was always observed in the pi gment epithelium at all stages analyzed but was extended to scattered cells located in the central portion of the neural retina around stage 22. The number of cells expressing Otx2 transcripts increased with ti me, following a central to peripheral gradient. Bromodeoxyuridine labe ling in combination with immunohistochemistry with anti-OTX2 antiserum and different cell-specific markers were used to determine that OTX2- positive cells are postmitotic neuroblasts undergoing differentiation into several, if not all, of the distinct cell types present in the ch ick retina. These data indicate that Otx2 might have a double role in eye development. First, it might be necessary for the early specificat ion and subsequent functioning of the pigment epithelium. Later, OTX2 expression might be involved in retina neurogenesis, defining a differ entiation feature common to the distinct retinal cell classes.