Role of Chromatin Remodelers in Retinal Regeneration

描述（由申请人提供）：在损伤或生长因子的作用下，鸡视网膜中的一些胶质细胞能够增殖、去分化为视网膜祖细胞并产生新的视网膜神经元。本研究将探讨神经胶质细胞表型可塑性的分子机制。在许多情况下，分化的能力取决于重塑染色质和激活分化特异性转录的能力。SWI/SNF染色质重塑复合体参与了多种分化过程，如肌肉形成、视网膜形成和脂肪形成。该提案将研究SWI/SNF在视网膜发育和再生中的潜在作用。具体目的包括：1)分析SWI/SNF在正常和再生视网膜中ATPase亚基的表达模式；2)确定ATPase亚基的活性是否对发育和再生是必要的；3)通过ChIP试验鉴定视网膜发生和视网膜再生过程中SWI/SNF调控的基因。更好地了解视网膜再生的机制将有助于黄斑变性和阿尔茨海默氏症等神经退行性疾病的治疗。

DESCRIPTION (provided by applicant): In response to damage or growth factors, some glia in the chick retina are capable of proliferation, dedifferentiation into retinal progenitors and the generation of new retinal neurons. This proposal will investigate the molecular mechanism of glia phenotypic plasticity. The ability to differentiate depends in many cases on the ability to remodel chromatin and activate differentiation specific transcription. The SWI/SNF chromatin remodeling complex has been implicated in several differentiation processes, such as myogenesis, retinogenesis, and adipogenesis. The proposal will investigate a potential role for SWI/SNF in retinal development and regeneration. The specific aims include 1) an analysis of the expression pattern of the ATPase subunits of SWI/SNF in normal and regenerating retina, 2) determining if the activity of the ATPase subunits are necessary for development and regeneration and 3) a ChIP assay to identify genes regulated by SWI/SNF during retinogenesis and retinal regeneration. A better understanding of the mechanism underlying retinal regeneration would aide in therapies for neurodegenerative diseases like macular degeneration and Alzheimer's.