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

Journal Article (Journal Article)

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 nonexcitable 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 thus neocortical neuron diversity.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • August 23, 2018

Published In

Volume / Issue

  • 174 / 5

Start / End Page

  • 1264 - 1276.e15

PubMed ID

  • 30057116

Pubmed Central ID

  • PMC6545245

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2018.06.036


  • eng

Conference Location

  • United States