Mutations in N-cadherin and a Stardust homolog, Nagie oko, affect cell-cycle exit in zebrafish retina

It has been reported that the loss of apicobasal cell polanty and the disruption of adherens junctions induce hyperplasia in the mouse developing brain However, it is not fully understood whether hyperplasia is caused by an enhanced cell proliferation, an inhibited neurogenesis, or both In this study, we found that the ratio of the number of proliferating progenitor cells to the total number of retinal cells increases in the neurogenic stages in zebrafish n-cadherin (ncad) and nagie oko (nok) mutants, in which the apicobasal cell polanty and adherens junctions in the retinal epithelium are disrupted The cell-cycle progression was not altered in the ncad and nok mutants Rather, the ratio of the number of cells undergoing neurogeinc cell division to the total number of cells undergoing mitosis decreased in the ncad and nok mutant retinas, suggesting that the switching from proliferative cell division to neurogenic cell division was compromised in these mutant retinas These findings suggest that the inhibition of neurogenesis is a primary defect that causes hyperplasia in the ncad and nok mutant retinas The Hedgehog-protein kinase A signaling pathway and the Notch signaling pathway regulate retinal neurogenesis in zebrafish We found that both signaling pathways are involved in the generation of neurogenic defects in the ncad and nok mutant retinas Taken together, these findings suggest that apicobasal cell polarity and epithelial integrity are essential for retinal neurogenesis in zebrafish (C) 2010 Elsevier Ireland Ltd All rights reserved