Zebrafish retinal development is linked to the differential expression of Vsx-1 and Vsx-2, paired-like:CVC homeobox genes that are characterized by a paired homeodomain and a conserved unique region termed the CVC domain. Vsx-2 expression is associated with proliferating neuroepithelial cells whereas Vsx-1 expression is associated with differentiation. This complementary expression suggests that Vsx-1 and Vsx-2 have different regulatory roles during the early stages of retinogenesis. In contrast, in the mature retina, both Vsx proteins co-localize in the upper tier of the inner nuclear layer (INL) suggesting that Vsx-1 and Vsx-2 have an additional role in maintaining differentiated bipolar cells. These results suggest that Vsx expression is essential for retinal development. Also, mice with a homozygous null allele for the mouse homologue of Vsx-2 (Chx10) show an ocular retardation phenotype, confirming the importance of paired-like:CVC homeobox function.
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The dynamic expression pattern of Vsx-1 correlates with cellular differentiation and lamination of the retina into distinct neuronal layers. In the mature retina, Vsx-1 is expressed in the bipolar cell layer. |
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In contrast to Vsx-1, Vsx-2 expression in the developing zebrafish retina is coincident with cellular proliferation. Vsx-2 expression decreases as cells in the neural retina differentiate. Vsx-2 expression is maintained in the mitotically active growth zone, located at the margin of the retina near the lens. In the mature eye, Vsx-2 expression co-localizes with Vsx-1 in the bipolar cell layer. |
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In COS-7 cells, as well as in vitro, Vsx-1 is conjugated with ubiquitin monomers that form ubiquitin chains. Such modification leads to the degradation of Vsx-1 in these cells and may regulate this protein during development. |
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In cultured cells, Vsx-1 localizes to the nucleus (green) whereas Plasticin B forms filaments in the cytoplasm. We are currently studying regulated import of Vsx-1 into the nucleus. |
