Sox11b regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish.

Sox11b regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish.
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DOI:
10.4103/1673-5374.346550
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发表时间:
2023-03
影响因子:
6.1
通讯作者:
Xu, Hui
Xu, Hui
中科院分区:
医学2区
文献类型:
--
作者:
Song, Kaida;Lin, Zihao;Cao, Lining;Lu, Bowen;Chen, Yuxi;Zhang, Shuqiang;Lu, Jianfeng;Xu, Hui

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转录因子 Sox11 在脊椎动物眼睛发育过程中的视网膜神经发生中发挥重要作用。然而,其在视网膜再生中的功能仍然难以捉摸。在这里,我们报道了斑马鱼 Sox11 同源物 Sox11b 在成年斑马鱼机械性视网膜损伤模型中调节 Müller 胶质细胞衍生祖细胞 (MGPC) 的迁移和命运决定。刺伤后,Sox11b 的表达在视网膜中增殖的 MGPC 中被诱导。尽管 MGPC 的核形态和随后的径向迁移发生了改变,但 Sox11b 敲低并不影响损伤后 4 天的 MGPC 形成。损伤后 7 天,与对照组相比,Sox11b 敲低导致视网膜内层 MGPC 比例增加,外核层 MGPC 比例减少。此外,Sox11b 敲低导致光感受器再生减少,同时增加了新生无长突和视网膜神经节细胞的数量。最后,定量聚合酶链反应分析表明,Sox11b 调节视网膜中 Notch 信号成分的表达,Notch 抑制部分重现了 Sox11b 敲低表型,表明 Notch 信号在 Sox11b 下游发挥作用。我们的研究结果表明,Sox11b 在斑马鱼视网膜再生过程中 MGPC 迁移和命运决定中发挥着关键作用,这可能对未来哺乳动物视网膜修复的探索具有重要意义。
The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development. However, its function in retina regeneration remains elusive. Here we report that Sox11b, a zebrafish Sox11 homolog, regulates the migration and fate determination of Müller glia-derived progenitors (MGPCs) in an adult zebrafish model of mechanical retinal injury. Following a stab injury, the expression of Sox11b was induced in proliferating MGPCs in the retina. Sox11b knockdown did not affect MGPC formation at 4 days post-injury, although the nuclear morphology and subsequent radial migration of MGPCs were altered. At 7 days post-injury, Sox11b knockdown resulted in an increased proportion of MGPCs in the inner retina and a decreased proportion of MGPCs in the outer nuclear layer, compared with controls. Furthermore, Sox11b knockdown led to reduced photoreceptor regeneration, while it increased the numbers of newborn amacrines and retinal ganglion cells. Finally, quantitative polymerase chain reaction analysis revealed that Sox11b regulated the expression of Notch signaling components in the retina, and Notch inhibition partially recapitulated the Sox11b knockdown phenotype, indicating that Notch signaling functions downstream of Sox11b. Our findings imply that Sox11b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish, which may have critical implications for future explorations of retinal repair in mammals.
DOI: 10.1016/j.expneurol.2011.10.005
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