Involvement of Numb in vertebrate retinal development: Evidence for multiple roles of Numb in neural differentiation and maturation
Involvement of Numb in vertebrate retinal development: Evidence for multiple roles of Numb in neural differentiation and maturation
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DOI：
10.1002/neu.10176
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发表时间：
2003-02-05
期刊：
影响因子：
--
通讯作者：
Ahmad, I
中科院分区：
文献类型：
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作者：
Dooley, CM;James, J;Ahmad, I
细胞命运特化部分由Notch信号传导介导的侧向抑制调节。Notch信号传导受Numb负调节，Numb是调节细胞能力的内在因子。在这项研究中，我们研究了Numb在视网膜发育中的参与，这已被证明受到Notch信号的影响。在发育中的视网膜中，Numb不对称地分布于不同细胞的脑室和玻璃体极。不对称定位是明显的，不仅在有丝分裂细胞，但在有丝分裂后的神经节细胞，以及，这表明亚细胞分布的Numb可能发挥作用后，细胞已退出细胞周期。这得到了成年视网膜中终末分化神经元中Numb表达的支持。虽然Numb是一个内在因素，但观察到其亚细胞分布受表观遗传线索的影响，使得在高密度培养的细胞中有更高比例的细胞不对称地表达Numb。观察到不对称定位和细胞能力之间的相关性; Numb不对称的细胞比对称表达Numb的细胞更容易在培养中分化。我们已经确定了替代剪接变异体在发展中国家和成人视网膜对应的亚型，已被证明可以调节增殖和分化。选择性剪接变体和亚型的动态时间表达模式表明，Numb可能会影响神经发生和有丝分裂后神经元成熟过程中视网膜祖细胞的增殖和分化。总之，这些结果证明了Numb在祖细胞和有丝分裂后神经元中分布的复杂作用。(C)2002 Wiley Periodicals，Inc.
Cell fate specification is regulated in part by lateral inhibition mediated by Notch signaling. Notch signaling is negatively regulated by Numb, an intrinsic factor that regulates cellular competence. In this study we have examined the involvement of Numb in retinal development, which has been shown to be influenced by Notch signaling. In the developing retina, Numb is asymmetrically distributed towards the ventricular and vitreal poles of different cells. Asymmetric localization is evident not only in mitotic cells but in postmitotic ganglion cells as well, suggesting that the subcellular distribution of Numb may play a role after cells have exited the cell cycle. This is supported by the expression of Numb in terminally differentiated neurons in the adult retina. Although Numb is an intrinsic factor, it is observed that its subcellular distribution is influenced by epigenetic cues such that a higher proportion of cells cultured at high density express Numb asymmetrically. A correlation is observed between asymmetric localization and cellular competence; cells in which Numb is asymmetric differentiate more readily in culture than those that express Numb symmetrically. We have identified alternative splice variants in the developing and adult retina that correspond to isoforms that have been shown to regulate proliferation and differentiation. The dynamic temporal expression patterns of alternative splice variants and isoforms suggest that Numb may influence proliferation and differentiation of retinal progenitors during neurogenesis and maturation of postmitotic neurons. Together, these results demonstrate the complex role of the distribution of Numb within progenitors and postmitotic neurons. (C) 2002 Wiley Periodicals, Inc.