The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration
The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration
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DOI：
10.1523/jneurosci.4853-07.2008
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发表时间：
2008-01-30
影响因子：
5.3
通讯作者：
Goldman, Daniel
中科院分区：
文献类型：
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作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
与哺乳动物不同，硬骨鱼可以再生受损的视网膜，恢复失去的视觉功能。对于视网膜再生的分子机制知之甚少。我们以前发现，在斑马鱼，视网膜损伤刺激穆勒神经胶质细胞产生多能α 1-微管蛋白（α 1 T）和pax 6表达的视网膜修复祖细胞。在这里，我们报告了一个关键的E-box在α 1 T启动子，介导的反式激活的achaete-scute复合物样1a（ascl 1a）在视网膜再生过程中的鉴定。更重要的是，我们发现ascl 1a对视网膜再生至关重要。在视网膜损伤后4小时内，在Muller胶质细胞中诱导ascl 1a。敲除asclla阻断α 1 T和pax 6的诱导以及Muller胶质细胞增殖，从而防止视网膜祖细胞及其分化后代的产生。这些数据表明，ascl 1a需要将静止的Muller胶质细胞转化为活跃分裂的视网膜祖细胞，并且ascl 1a是启动视网膜再生的关键调节因子。
Unlike mammals, teleost fish can regenerate an injured retina, restoring lost visual function. Little is known of the molecular events that underlie retina regeneration. We previously found that in zebrafish, retinal injury stimulates Muller glia to generate multipotent alpha 1-tubulin (alpha 1T) and pax6-expressing progenitors for retinal repair. Here, we report the identification of a critical E-box in the alpha 1T promoter that mediates transactivation by achaete-scute complex-like 1a (ascl1a) during retina regeneration. More importantly, we show that ascl1a is essential for retina regeneration. Within 4 h after retinal injury, ascl1a is induced in Muller glia. Knockdown of ascl1a blocks the induction of alpha 1T and pax6 as well as Muller glial proliferation, consequently preventing the generation of retinal progenitors and their differentiated progeny. These data suggest ascl1a is required to convert quiescent Muller glia into actively dividing retinal progenitors, and that ascl1a is a key regulator in initiating retina regeneration.