Cadherin-6 function in zebrafish retinal development

Cadherin cell-adhesion molecules play crucial roles in vertebrate development including the development of the visual system. Most studies have focused on examining functions of classical type I cadherins (e.g., cadherin-2) in visual system development. There is little information on the function of classical type II cadherins (e.g., cadherin-6) in the development of the vertebrate visual system. To gain insight into cadherin-6 role in the formation of the retina, we analyzed differentiation of retinal ganglion cells (RGCs), amacrine cells, and photoreceptors in zebrafish embryos injected with cadherin-6 specific antisense morpholino oligonucleotides. Differentiation of the retinal neurons in cadherin-6 knockdown embryos (cdh6 morphants) was analyzed using multiple markers. We found that expression of transcription factors important for retinal development was greatly reduced, and expression of Notch-Delta genes and proneural gene ath5 was altered in the cdh6 morphant retina. The retinal lamination was present in the morphants, although the morphant eyes were significantly smaller than control embryos due mainly to decreased cell proliferation. Differentiation of the RGCs, amacrine cells, and photoreceptors was severely disrupted in the cdh6 morphants due to a significant delay in neural differentiation. Our results suggest that cadherin-6 plays an important role in the normal formation of the zebrafish retina.