Pax6a and Pax6b are required at different points in neuronal progenitor cell proliferation during zebrafish photoreceptor regeneration.
Pax6a and Pax6b are required at different points in neuronal progenitor cell proliferation during zebrafish photoreceptor regeneration.
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DOI：
10.1016/j.exer.2010.02.001
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发表时间：
2010-05
影响因子：
3.4
通讯作者：
Hyde, David R.
中科院分区：
文献类型：
--
作者：
Thummel, Ryan;Enright, Jennifer M.;Kassen, Sean C.;Montgomery, Jacob E.;Bailey, Travis J.;Hyde, David R.
光损伤的斑马鱼视网膜导致光感受器细胞死亡，随后缺失的视杆细胞和视锥细胞再生。光感受器再生开始于不对称的m<s:1>神经胶质细胞分裂，产生神经元祖细胞，这些细胞扩增，迁移到外核层（ONL），并分化为两类光感受器细胞。在这项研究中，我们检测了Pax6蛋白在再生中的作用。斑马鱼体内有两种Pax6蛋白，一种由pax6a基因编码，另一种由pax6b基因编码。我们通过玻璃体内注射和电穿孔与pax6a或pax6b mRNA互补的morpholinos来敲除相应蛋白的翻译。Pax6b表达的缺失不影响<s:2>神经胶质细胞的分裂，但阻断了神经元祖细胞随后的第一次细胞分裂。与此相反，Pax6a蛋白在后期的神经祖细胞分裂中是必需的，这使得神经祖细胞的数量最大化。在不扩增神经元祖细胞的情况下，只能再生杆状细胞的ONL杆前体细胞增殖与INL神经元祖细胞数量成反比。这证实了<s:1>勒神经胶质来源的神经元祖细胞是再生视锥细胞所必需的，并且有不同的机制选择性地再生视杆和视锥光感受器。这项工作还定义了Pax6a和Pax6b在调节成年斑马鱼视网膜中神经元祖细胞增殖中的不同作用，并增加了我们对光感受器细胞再生所需的分子途径的理解。
The light-damaged zebrafish retina results in the death of photoreceptor cells and the subsequent regeneration of the missing rod and cone cells. Photoreceptor regeneration initiates with asymmetric Müller glial cell division to produce neuronal progenitor cells, which amplify, migrate to the outer nuclear layer (ONL), and differentiate into both classes of photoreceptor cells. In this study, we examined the role of the Pax6 protein in regeneration. In zebrafish, there are two Pax6 proteins, one encoded by the pax6a gene and the other encoded by the pax6b gene. We intravitreally injected and electroporated morpholinos that were complementary to either the pax6a or pax6b mRNA to knockdown the translation of the corresponding protein. Loss of Pax6b expression did not affect Müller glial cell division, but blocked the subsequent first cell division of the neuronal progenitors. In contrast, the paralogous Pax6a protein was required for later neuronal progenitor cell divisions, which maximized the number of neuronal progenitors. Without neuronal progenitor cell amplification, proliferation of resident ONL rod precursor cells, which can only regenerate rods, increased inversely proportional to the number of INL neuronal progenitor cells. This confirmed that Müller glial-derived neuronal progenitor cells are necessary to regenerate cones and that distinct mechanisms selectively regenerate rod and cone photoreceptors. This work also defines distinct roles for Pax6a and Pax6b in regulating neuronal progenitor cell proliferation in the adult zebrafish retina and increases our understanding of the molecular pathways required for photoreceptor cell regeneration.
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影响因子：
5.3
作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
通讯作者：
Goldman, Daniel
影响因子：
4.4
作者：
Morris, AC;Schroeter, EH;Fadool, JM
通讯作者：
Fadool, JM
影响因子：
2.7
作者：
Rowan, S;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
4.6
作者：
Blader, P;Lam, CS;Str채hle, U
通讯作者：
Str채hle, U
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.