Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors.
Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors.
复制标题
麻痹性果蝇电压门控钠通道调节神经祖细胞的增殖。
DOI：
10.1101/gad.330597.119
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发表时间：
2019
影响因子：
10.5
通讯作者：
Jan,YuhNung
中科院分区：
文献类型：
--
作者：
Piggott,BeverlyJ;Peters,ChristianJ;He,Ye;Huang,Xi;Younger,Susan;Jan,LilyYeh;Jan,YuhNung
然而，通常被认为是“不可兴奋”的兴奋细胞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，并在癌症中上调。在这里，我们确定了VGSC在果蝇神经母细胞（NB）谱系在中枢神经系统内的增殖中的作用。缺失编码果蝇VGSC的唯一基因paralytic（帕拉），可减少神经母细胞后代细胞数量。II型神经母细胞谱系，具有类似于在发育中的人类皮质中发现的过渡扩增中间神经祖细胞（INP）的群体，对帕拉操纵特别敏感。在一系列不对称分裂之后，INPs通常通过最终的对称分裂退出细胞周期。我们的数据表明，帕拉的损失诱导细胞凋亡，在这个群体中，而过度表达导致增加INPs和整体神经母细胞后代细胞数量。这些效应是细胞自主的，并且依赖于帕拉通道活性。帕拉表达的降低不仅影响正常NB的发展，而且强烈抑制脑肿瘤质量，暗示了帕拉在癌症进展中的作用。据我们所知，我们的研究是第一个确定VGSC在神经祖细胞增殖中的作用。阐明VGSC在增殖中的贡献将促进我们对发育和疾病状态中生物电信号的理解。
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.