Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells
Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells
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DOI：
10.1523/jneurosci.1624-07.2007
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发表时间：
2007-06-27
影响因子：
5.3
通讯作者：
Raymond, Pamela A.
中科院分区：
文献类型：
--
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
哺乳动物脑中的神经元祖细胞来源于放射状胶质细胞或特化的星形胶质细胞。在发育中的神经视网膜中，放射状胶质样Muller细胞在神经发生的后期产生，并且不被认为是神经元祖细胞，但它们在损伤后确实增殖，并且可以表达神经元标记物，这表明潜在的神经发生能力。为了研究视网膜神经胶质细胞的神经发生能力，我们在转基因斑马鱼中使用谱系追踪，该转基因斑马鱼具有胶质细胞特异性启动子（gfap，用于胶质细胞酸性蛋白），其在分化的Mur ller胶质细胞中驱动绿色荧光蛋白。我们发现，斑马鱼视网膜中的所有Muller神经胶质细胞表达低水平的多能祖标记Pax 6（配对盒基因6），并且它们在完整的未受伤的视网膜中以低频率增殖。Muller胶质细胞衍生的祖细胞表达Crx（视锥-视杆同源盒），并且是在胚后视网膜中产生视杆光感受器谱系的晚期视网膜祖细胞。这些Muller神经胶质衍生的祖细胞也仍然能够产生早期的神经元谱系，因为它们通过特异性地再生缺失的神经元来响应视锥光感受器的损失。我们的结论是，斑马鱼Muller胶质细胞作为多能视网膜干细胞，通过稳态和再生发育机制产生视网膜神经元。
Neuronal progenitors in the mammalian brain derive from radial glia or specialized astrocytes. In developing neural retina, radial glia-like Muller cells are generated late in neurogenesis and are not considered to be neuronal progenitors, but they do proliferate after injury and can express neuronal markers, suggesting a latent neurogenic capacity. To examine the neurogenic capacity of retinal glial cells, we used lineage tracing in transgenic zebrafish with a glial-specific promoter (gfap, for glial fibrillary acid protein) driving green fluorescent protein in differentiated Mu r ller glia. We found that all Muller glia in the zebrafish retina express low levels of the multipotent progenitor marker Pax6 (paired box gene 6), and they proliferate at a low frequency in the intact, uninjured retina. Muller glia-derived progenitors express Crx (cone rod homeobox) and are late retinal progenitors that generate the rod photoreceptor lineage in the postembryonic retina. These Muller glia-derived progenitors also remain competent to produce earlier neuronal lineages, in that they respond to loss of cone photoreceptors by specifically regenerating the missing neurons. We conclude that zebrafish Muller glia function as multipotent retinal stem cells that generate retinal neurons by homeostatic and regenerative developmental mechanisms.