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Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors.
Genes & development Pub Date : 2019-11-21 , DOI: 10.1101/gad.330597.119
Beverly J Piggott 1, 2 , Christian J Peters 1 , Ye He 3 , Xi Huang 4, 5, 6 , Susan Younger 1, 2 , Lily Yeh Jan 1, 2 , Yuh Nung Jan 1, 2
Affiliation  

Proliferating cells, typically considered "nonexcitable," nevertheless, exhibit regulation by bioelectric signals. Notably, voltage-gated sodium channels (VGSC) that are crucial for neuronal excitability are also found in progenitors and up-regulated in cancer. Here, we identify a role for VGSC in proliferation of Drosophila neuroblast (NB) lineages within the central nervous system. Loss of paralytic (para), the sole gene that encodes Drosophila VGSC, reduces neuroblast progeny cell number. The type II neuroblast lineages, featuring a population of transit-amplifying intermediate neural progenitors (INP) similar to that found in the developing human cortex, are particularly sensitive to para manipulation. Following a series of asymmetric divisions, INPs normally exit the cell cycle through a final symmetric division. Our data suggests that loss of Para induces apoptosis in this population, whereas overexpression leads to an increase in INPs and overall neuroblast progeny cell numbers. These effects are cell autonomous and depend on Para channel activity. Reduction of Para expression not only affects normal NB development, but also strongly suppresses brain tumor mass, implicating a role for Para in cancer progression. To our knowledge, our studies are the first to identify a role for VGSC in neural progenitor proliferation. Elucidating the contribution of VGSC in proliferation will advance our understanding of bioelectric signaling within development and disease states.

中文翻译:


麻痹性果蝇电压门控钠通道可调节神经祖细胞的增殖。



然而,通常被认为“不可兴奋”的增殖细胞却表现出生物电信号的调节。值得注意的是,对神经元兴奋性至关重要的电压门控钠通道(VGSC)也存在于祖细胞中,并且在癌症中表达上调。在这里,我们确定了 VGSC 在中枢神经系统内果蝇成神经细胞 (NB) 谱系增殖中的作用。编码果蝇 VGSC 的唯一基因 paralytic (para) 的缺失会减少神经母细胞后代细胞数量。 II 型神经母细胞谱系的特点是具有与发育中的人类皮层中发现的类似的转运放大中间神经祖细胞 (INP) 群体,对副操纵特别敏感。经过一系列不对称分裂后,INP 通常通过最终的对称分裂退出细胞周期。我们的数据表明,Para 的缺失会诱导该群体的细胞凋亡,而过度表达会导致 INP 和神经母细胞后代细胞总数的增加。这些效应是细胞自主的并且取决于副通道活性。 Para 表达的减少不仅影响正常的 NB 发育,而且还强烈抑制脑肿瘤质量,表明 Para 在癌症进展中的作用。据我们所知,我们的研究首次确定了 VGSC 在神经祖细胞增殖中的作用。阐明 VGSC 在增殖中的贡献将增进我们对发育和疾病状态中生物电信号传导的理解。
更新日期:2019-11-01
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