Proper differentiation of photoreceptors and amacrine cells depends on a regulatory loop between NeuroD and Six6

• DOI: 10.1242/dev.045294
• Publication Date: 2010-06-10T00:46:02Z
• Authors: Ivan Conte; Raquel Marco-Ferr...; Leonardo Beccari; Elsa Cisneros; José María Ruiz; Noemí Tabanera; Paola Bovolenta
• Keywords: NeuroD; Recoverin; Ganglion cell layer

Timely generation of distinct neural cell types in appropriate numbers is fundamental for the a functional retina. In vertebrates, transcription factor Six6 initially expressed multipotent retina progenitors and then becomes restricted to differentiated retinal ganglion amacrine cells. How expression controlled what are its precise functions still unclear. To address this issue, we used bioinformatic searches transgenic approaches medaka fish (Oryzias latipes) characterise highly conserved regulatory enhancers responsible expression. One drove gene differentiating adult A search binding sites, together with luciferase, ChIP assays gain-of-function studies, indicated that NeuroD, bHLH factor, directly binds an 'E-box' sequence present enhancer specifically regulates NeuroD-induced overexpression embryos promoted unorganized progenitor proliferation and, most notably, impaired photoreceptor differentiation, no apparent changes other types. Conversely, gain- loss-of-function changed NeuroD levels altered differentiation marker Rhodopsin. addition, knockdown interfered generation. Together, these results indicate control each their coordinate terminal differentiation.