Progenitor Hyperpolarization Regulates the Sequential Generation of Neuronal Subtypes in the Developing Neocortex.

Progenitor Hyperpolarization Regulates the Sequential Generation of Neuronal Subtypes in the Developing Neocortex.
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DOI:
10.1016/j.cell.2018.06.036
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发表时间:
2018-08-23
期刊:
影响因子:
64.5
通讯作者:
Jabaudon D
Jabaudon D
中科院分区:
生物学1区
文献类型:
--
作者:
Vitali I;Fièvre S;Telley L;Oberst P;Bariselli S;Frangeul L;Baumann N;McMahon JJ;Klingler E;Bocchi R;Kiss JZ;Bellone C;Silver DL;Jabaudon D

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During corticogenesis, ventricular zone progenitors sequentially generate distinct subtypes of neurons, accounting for the diversity of neocortical cells and the circuits they form. While activity-dependent processes are critical for the differentiation and circuit assembly of postmitotic neurons, how bioelectrical processes affect non-excitable cells such as progenitors remains largely unknown. Here, we reveal that, in the developing mouse neocortex, ventricular zone progenitors become more hyperpolarized as they generate successive subtypes of neurons. Experimental in vivo hyperpolarization shifted the transcriptional programs and division modes of these progenitors to a later developmental status, with precocious generation of intermediate progenitors and a forward shift in the laminar, molecular, morphological and circuit features of their neuronal progeny. These effects occurred through inhibition of the Wnt-beta-catenin signaling pathway by hyperpolarization. Thus, during corticogenesis, bioelectric membrane properties are permissive for specific molecular pathways to coordinate the temporal progression of progenitor developmental programs and hence neocortical neuron diversity. Progressive changes in the membrane potential of neural progenitors during corticogenesis coordinates the temporal progression of neuronal subtype specification in neocortex.
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