Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina
Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina
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DOI：
10.1016/j.neuron.2005.09.030
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发表时间：
2005-11-23
期刊：
影响因子：
16.2
通讯作者：
Knoblich, JA
中科院分区：
文献类型：
--
作者：
Zigman, M;Cayouette, M;Knoblich, JA
在哺乳动物神经发生过程中，祖细胞分裂时纺锤体平行或垂直于神经上皮表面。垂直分裂更可能是不对称的，产生一个祖细胞和一个神经元前体。是否有丝分裂纺锤体的方向实际上决定了它们的不对称结果尚不清楚。在这里，我们描述了一个哺乳动物同源的incuteable (mlnsc)，果蝇纺锤体取向的关键调节因子。MLNSC在时间和空间上的表达方式表明在发育中的神经系统中有丝分裂纺锤体的定向作用。在大鼠视网膜外植体中使用逆转录病毒RNAi，我们发现mlnsc的下调抑制了垂直分裂。这导致增殖增强，与对称分裂产生两个增殖细胞的频率较高一致。我们的研究结果表明，神经祖细胞分裂的方向对视网膜细胞命运规范很重要，并决定了它们的对称或不对称结果。
During mammalian neurogenesis, progenitor cells can divide with the mitotic spindle oriented parallel or perpendicular to the surface of the neuroepithelium. Perpendicular divisions are more likely to be asymmetric and generate one progenitor and one neuronal precursor. Whether the orientation of the mitotic spindle actually determines their asymmetric outcome is unclear. Here, we characterize a mammalian homolog of Inscuteable (mlnsc), a key regulator of spindle orientation in Drosophila. mlnsc is expressed temporally and spatially in a manner that suggests a role in orienting the mitotic spindle in the developing nervous system. Using retroviral RNAi in rat retinal explants, we show that downregulation of mlnsc inhibits vertical divisions. This results in enhanced proliferation, consistent with a higher frequency of symmetric divisions generating two proliferating cells. Our results suggest that the orientation of neural progenitor divisions is important for cell fate specification in the retina and determines their symmetric or asymmetric outcome.