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R.A. Martins, S.L. Donovan, F. Zindy, M. Roussel, M.A. Dyer; Nmyc Is Required For Proper Retinal Growth In Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4193.
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Nmyc (Nmyc1) is a member of a family of proto–oncogenes (Myc, Lmyc and Nmyc) encoding basic helix–loop–helix– leucine zipper (bHLHZ) proteins. These proteins act as transcriptional regulators that regulate the expression of a very large number of genes important for cell proliferation and cell death. Previous studies have demonstrated that Nmyc is essential for normal neurogenesis of the cerebellum.
In this work, we asked whether Nmyc regulates mouse retinal development.
Nmyc gene expression was determined by realtime RT–PCR and Nmyc protein was analyzed by immunohistochemistry. To determine the role of Nmyc in retinal development, we have analyzed a combination of genetics approaches, including Cre–transgenic mouse lines and Cre–expressing retrovirus. Analysis includes immunofluorescence with various antibodies to cell type specific proteins, proliferation analysis with Brdu and cell death analysis by different methods including TUNEL.
Nmyc is highly expressed in retinal progenitor cells during embryonic and postnatal retinal development. Adult retina from Nmyc–null mice exibit a drastic reduction in size, and interestingly we found that most of retinal cell types are generated in the correct proportion. This phenotype is distinct from other hypoplastic retinae, such as cyclin D1 deficient or Chx10 deficient mice. Preliminary data suggests that genetic inactivation of p19Ink4d and/or p27Kip1, the major cyclin kinase inhibitors in the mouse retina, rescued Nmyc phenotype. Inactivation of p18 Ink4c which is not expressed in the mouse retina had no effect on the Nmyc phenotype.
Based on our data, we propose that Nmyc is an important regulator of progenitor retinal cells proliferation during development.
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