Loss of adenomatous polyposis coli (apc) Results in an Expanded Ciliary Marginal Zone in the Zebrafish Eye

The distal region of neural retina (ciliary marginal zone [CMZ]) contains stem cells that produce non-neural and neuronal progenitors. We provide a detailed gene expression analysis of the eyes of ape mutant zebrafish where the Wnt/beta-catenin pathway is constitutively active. Wnt/beta-catenin signaling leads to an expansion of the CMZ accompanied by a central shift of the retinal identity gene sox2 and the proneural gene atoh7. This suggests an important role for peripheral Wnt/beta-catenin signaling in regulating the expression and localization of neurogenic genes in the central retina. Retinal identity genes rx1 and vsx2, as well as meis1 and pax6a act upstream of Wnt/beta-catenin pathway activation. Peripheral cells that likely contain stem cells can be identified by the expression of follistatin, otx1, and axin2 and the lack of expression of myca and cyclinD1. Our results introduce the zebrafish ape mutation as a new model to study signaling pathways regulating the CMZ. Developmental Dynamics 239:2066-2077, 2010. (C) 2010 Wiley-Liss, Inc.