Using myc genes to search for stem cells in the ciliary margin of the Xenopus retina.

The ciliary marginal zone (CMZ) of fish and frog retinas contains cells that proliferate throughout postembryonic development as the retina grows with increasing body size, indicating the presence of stem cells in this region. However, neither the location nor the molecular identity of retinal stem cells has been identified. Here, we show in Xenopus that c-myc and n-myc are sequentially expressed both during development and in the post-embryonic retina. The c-myc+/n-myc- cells near the extreme periphery of the CMZ cycle more slowly and preferentially retain DNA label compared to their more central cmyc+/n-myc+ neighbors which cycle rapidly and preferentially dilute DNA label. During retinal development c-myc is functionally required earlier than n-myc, and n-myc expression depends on earlier c-myc expression. The expression of c-myc but not n-myc in the CMZ depends on growth factor signaling. Our results suggest that c-myc+/n-myc- cells in the far peripheral CMZ are candidates for a niche-dependent population of retinal stem cells that give rise to more centrally located and rapidly dividing n-myc+ progenitors of more limited proliferative potential. Analysis of homologues of these genes in the zebrafish CMZ suggests that the transition from c-myc to n-myc expression might be conserved in other lower vertebrates whose retinas growth throughout life.