中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 445-450.doi: 10.4103/1673-5374.346550

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

Sox11b可调节斑马鱼视网膜再生过程中 Müller 胶质祖细胞的迁移和命运

  

  • 出版日期:2023-02-15 发布日期:2022-08-09
  • 基金资助:
    国家重点研发计划项目(2017YFA0104100,2017YFA0701304);国家自然科学基金项目(81970820,31930068)

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

Kaida Song1, #, Zihao Lin1, #, Lining Cao2, #, Bowen Lu1, Yuxi Chen1, Shuqiang Zhang1, Jianfeng Lu2, *, Hui Xu1, *   

  1. 1Key Lab of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu Province, China; 2Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
  • Online:2023-02-15 Published:2022-08-09
  • Contact: Hui Xu, MD, PhD, huixu82@126.com; Jianfeng Lu, PhD, lu.jianfeng@tongji.edu.cn.
  • Supported by:
    This work was supported by the National Key Research and Development Project of China, Nos. 2017YFA0104100 (to JL), 2017YFA0701304 (to HX); and National Natural Science Foundation of China Nos. 81970820 (to HX), 31930068 (to JL).

摘要:

转录因子Sox11可在脊椎动物视网膜发育过程中起重要作用,但其在视网膜再生中的作用仍然难以捉摸。此次实验发现针刺斑马鱼的机械性视网膜损伤,可诱导增殖的Müller胶质源性祖细胞中Sox11同源物 Sox11b的表达。(1)Sox11b 敲低虽不影响损伤后4 d时的Müller胶质源性祖细胞的增殖,但会改变后者的核形态和径向迁移。Sox11b敲低会导致损伤后7 d时视网膜内层 Müller胶质源性祖细胞比例增加,外核层Müller胶质源性祖细胞比例降低。因此,Sox11b敲低可减少光感受器再生,而再生后的无长突和神经节细胞增多。(2)定量聚合酶链式反应进一步发现Sox11b可调节视网膜中Notch信号因子的表达,而抑制Notch可部分复制Sox11b敲低的表型,提示Notch是其下游通路。(3)实验结果显示Sox11b可在斑马鱼视网膜再生过程中Müller胶质源性祖细胞迁移和命运决定中起作用,这可能对未来的哺乳动物视网膜修复具有深入研究探讨其价值的意义。

https://orcid.org/0000-0003-0782-4160 (Hui Xu); https://orcid.org/0000-0003-0547-0450 (Jianfeng Lu)

关键词: Sox11, Müller细胞, Müller胶质细胞来源祖细胞, 细胞迁移, 命运决定, 感光器, 视网膜再生, 斑马鱼转录因子, Notch信号

Abstract: 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.

Key words: cell migration, fate determination, Müller glia, Müller glia-derived progenitor, Notch signaling, photoreceptor, retina regeneration, Sox11, transcription factor, zebrafish