Sox2 regulates Müller glia reprogramming and proliferation in the regenerating zebrafish retina via Lin28 and Ascl1a.
Sox2 regulates Müller glia reprogramming and proliferation in the regenerating zebrafish retina via Lin28 and Ascl1a.
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DOI：
10.1016/j.exer.2017.05.012
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发表时间：
2017-08
影响因子：
3.4
通讯作者：
Hyde DR
中科院分区：
文献类型：
--
作者：
Gorsuch RA;Lahne M;Yarka CE;Petravick ME;Li J;Hyde DR
Sox2是一种成熟的神经干细胞相关转录因子，调节脊椎动物神经发育和成体神经发生，是将分化细胞重编程为诱导多能干细胞的关键基因之一。我们研究了Sox2是否参与早期重编程样事件，即在光损伤的成年斑马鱼视网膜中，神经胶质细胞上调增殖所需的许多多能性和神经干细胞相关基因。在未受损的成年斑马鱼视网膜中，Sox2在神经胶质细胞和无突细胞亚群中表达，与其他脊椎动物相似。光损伤31小时后，Sox2在增殖的神经胶质细胞中表达显著增加。morpholino介导的Sox2表达下调导致增殖的神经神经胶质细胞数量减少，而诱导的Sox2过表达则在没有视网膜损伤的情况下刺激神经神经胶质细胞增殖。因此，Sox2是神经胶质细胞增殖的必要和充分条件。我们研究了Wnt/β-catenin信号的作用，它是脊椎动物视网膜发育过程中sox2表达的已知调节因子。虽然β-catenin 2，而不是β-catenin 1，是<s:1> ller胶质细胞增殖所必需的，但视网膜损伤后sox2的表达都不需要β-catenin平行体。ascl1a（神经源性）和lin28a（重编程）表达也需要Sox2表达，但视网膜损伤后stat3表达不需要Sox2表达。此外，Sox2是<s:1> ller胶质源性神经祖细胞扩增和前神经标记物Tg（atoh7:EGFP）表达所必需的。最后，Sox2表达的缺失阻碍了视锥光感受器的完全再生。这项研究首次确定了Sox2在脊椎动物视网膜神经胶质再生过程中的功能作用。
Sox2 is a well-established neuronal stem cell-associated transcription factor that regulates neural development and adult neurogenesis in vertebrates, and is one of the critical genes used to reprogram differentiated cells into induced pluripotent stem cells. We examined if Sox2 was involved in the early reprogramming-like events that Müller glia undergo as they upregulate many pluripotency- and neural stem cell-associated genes required for proliferation in light-damaged adult zebrafish retinas. In the undamaged adult zebrafish retina, Sox2 is expressed in Müller glia and a subset of amacrine cells, similar to other vertebrates. Following 31 hours of light damage, Sox2 expression significantly increased in proliferating Müller glia. Morpholino-mediated knockdown of Sox2 expression resulted in decreased numbers of proliferating Müller glia, while induced overexpression of Sox2 stimulated Müller glia proliferation in the absence of retinal damage. Thus, Sox2 is necessary and sufficient for Müller glia proliferation. We investigated the role of Wnt/β-catenin signaling, which is a known regulator of sox2 expression during vertebrate retinal development. While β-catenin 2, but not β-catenin 1, was necessary for Müller glia proliferation, neither β-catenin paralog was required for sox2 expression following retinal damage. Sox2 expression was also necessary for ascl1a (neurogenic) and lin28a (reprogramming) expression, but not stat3 expression following retinal damage. Furthermore, Sox2 was required for Müller glial-derived neuronal progenitor cell amplification and expression of the pro-neural marker Tg(atoh7:EGFP). Finally, loss of Sox2 expression prevented complete regeneration of cone photoreceptors. This study is the first to identify a functional role for Sox2 during Müller glial-based regeneration of the vertebrate retina.
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影响因子：
4.4
作者：
Bachleda AR;Pevny LH;Weiss ER
通讯作者：
Weiss ER
影响因子：
2.7
作者：
Millimaki BB;Sweet EM;Riley BB
通讯作者：
Riley BB
DOI：
10.1002/cne.22243
发表时间：
2010-03-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Montgomery JE;Parsons MJ;Hyde DR
通讯作者：
Hyde DR
影响因子：
5.3
作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
通讯作者：
Goldman, Daniel
DOI：
10.1073/pnas.1220176110
发表时间：
2013-08-06
影响因子：
11.1
作者：
Cimadamore, Flavio;Amador-Arjona, Alejandro;Terskikh, Alexey V.
通讯作者：
Terskikh, Alexey V.