Lin28a regulates neurogliogenesis in mammalian retina through the Igf signaling.
Lin28a regulates neurogliogenesis in mammalian retina through the Igf signaling.
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DOI：
10.1016/j.ydbio.2018.05.007
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发表时间：
2018-08
影响因子：
2.7
通讯作者：
Xiaohuan Xia;Pooja Teotia;I. Ahmad
中科院分区：
文献类型：
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作者：
Xiaohuan Xia;Pooja Teotia;I. Ahmad
在发育中的中枢神经系统（CNS）中，大多数神经元在胶质细胞产生之前就已经产生。新的证据表明，异时基因Lin 28在两个不同谱系之间的时间转换中起作用。然而，Lin 28 a和Lin 28 b各自的神经胶质形成的贡献仍然知之甚少。在此，我们研究了Lin 28 a和Lin 28在哺乳动物视网膜中的相对参与，这是一种简单易行的CNS模型，神经胶质生成决定主要发生在出生后。通过功能扰动方法对晚期组织发生过程中Lin 28 a/B参与的检查显示，虽然Lin 28 B一般不影响分化，但Lin 28 a分别促进和拮抗神经元和胶质细胞的生成。Lin 28 a在体外表达的沉默和其在体内组织发生早期的条件性缺失导致胶质细胞的过早产生。Lin 28 a对神经元分化的指导作用通过其抑制胶质细胞特异性基因和直接沿着神经元谱系分化胶质细胞的影响来揭示。Lin 28 a的这种功能可能是通过Igf信号传导介导的，因为抑制该途径消除了Lin 28 a介导的神经胶质细胞生成。因此，我们的观察结果表明，Lin 28 a是一个重要的内在因素，与细胞的外在因素，如IGFS，协调的祖细胞和生态位，分别为连续一代的神经元和神经胶质细胞的发展偏见。
In the developing central nervous system (CNS) the majority of neurons are born before the generation of glia. Emerging evidence implicates heterochronic gene,Lin28in the temporal switch between two distinct lineages. However, the respective contributions ofLin28aandLin28bin neurogliogenesis remain poorly understood. Here, we have examined the relative involvement ofLin28aandLin28bin mammalian retina, a simple and accessible CNS model where neurogliogenic decision largely occurs postnatally. Examination of Lin28a/b involvement during late histogenesis by the perturbation of function approaches revealed that while Lin28b did not influence differentiation in general Lin28a facilitated and antagonized the generation of neurons and glia, respectively. Silencing of Lin28a expression in vitro and its conditional deletion in vivo during early histogenesis led to premature generation of glia. The instructive role of Lin28a on neuronal differentiation was revealed by its influence to suppress glial-specific genes and directly differentiate glia along the neuronal lineage. This function of Lin28a is likely mediated through the Igf signaling, as inhibition of the pathway abrogated Lin28a-mediated neurogliogenesis. Thus, our observations suggest that Lin28a is an important intrinsic factor that acts in concert with cell-extrinsic factors like Igfs, coordinating the developmental bias of the progenitors and niche, respectively, for the successive generation of neurons and glia.