Cell-Intrinsic Control of Interneuron Migration Drives Cortical Morphogenesis

Carla G. Silva, Elise Peyre, Mohit H. Adhikari, Sylvia Tielens, Sebastian Tanco, Petra Van Damme, Lorenza Magno, Nathalie Krusy, Gulistan Agirman, Maria M. Magiera, Nicoletta Kessaris, Brigitte Malgrange, Annie Andrieux, Carsten Janke, Laurent Nguyen*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

Abstract

Interneurons navigate along multiple tangential paths to settle into appropriate cortical layers. They undergo a saltatory migration paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. It remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes post-translational protein deglutamylation, controls the pausing of migrating cortical interneurons. Moreover, we demonstrate that pausing during migration attenuates movement simultaneity at the population level, thereby controlling the flow of interneurons invading the cortex. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also impairs the generation of age-matched projection neurons of the upper layers. The “stop and go” movement of individual migrating cortical interneurons is critical for ensuring a proper rate of cortical invasion for the entire population.

Original languageEnglish
Pages (from-to)1063-1078.e19
Number of pages36
JournalCell
Volume172
Issue number5
DOIs
Publication statusPublished - 22 Feb 2018

Keywords

  • actomyosin
  • carboxypeptidase
  • corticogenesis
  • cytoskeleton
  • glutamylation
  • MLCK
  • neurogenesis

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