{"id":5293,"date":"2019-03-04T16:06:54","date_gmt":"2019-03-04T22:06:54","guid":{"rendered":"https:\/\/irrf.org\/?p=5293"},"modified":"2023-10-04T16:13:01","modified_gmt":"2023-10-04T21:13:01","slug":"smc1-and-the-cohesin-complex-in-retinal-development-and-disease","status":"publish","type":"post","link":"https:\/\/irrf.org\/smc1-and-the-cohesin-complex-in-retinal-development-and-disease\/","title":{"rendered":"Smc1 and the Cohesin Complex in Retinal Development and Disease"},"content":{"rendered":"\r\n
PROJECT TITLE:<\/strong> Smc1 and the Cohesin Complex in Retinal Development and Disease: A New Mouse Model of Photoreceptor Degeneration<\/em> ABSTRACT<\/strong>: Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood.\u00a0 This study found that c-myc regulates cell proliferation in\u00a0 mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens.\u00a0 The role of N-myc was examined in mouse lens development.\u00a0 Genetic inaction of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while \u201clate\u201d inactivation in lens fibers had no effect.\u00a0 Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival.\u00a0 Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells.\u00a0 RNA-sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseII\u03b2.\u00a0 Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens.\u00a0 Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage.\u00a0 Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis.<\/p>\r\n\r\n\r\n\r\n