Insm1 Induces Neural Progenitor Delamination in Developing Neocortex via Downregulation of the Adherens Junction Belt-Specific Protein Plekha7

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Stefania Tavano - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Elena Taverna - , Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Institute for Evolutionary Anthropology (Author)
  • Nereo Kalebic - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Christiane Haffner - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Takashi Namba - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Andreas Dahl - , DRESDEN-concept Genome Center (CMCB Core Facility) (Author)
  • Michaela Wilsch-Bräuninger - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Judith T.M.L. Paridaen - , Max Planck Institute of Molecular Cell Biology and Genetics, University of Groningen (Author)
  • Wieland B. Huttner - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)

Abstract

Delamination of neural progenitor cells (NPCs) from the ventricular surface is a crucial prerequisite to form the subventricular zone, the germinal layer linked to the expansion of the mammalian neocortex in development and evolution. Here, we dissect the molecular mechanism by which the transcription factor Insm1 promotes the generation of basal progenitors (BPs). Insm1 protein is most highly expressed in newborn BPs in mouse and human developing neocortex. Forced Insm1 expression in embryonic mouse neocortex causes NPC delamination, converting apical to basal radial glia. Insm1 represses the expression of the apical adherens junction belt-specific protein Plekha7. CRISPR/Cas9-mediated disruption of Plekha7 expression suffices to cause NPC delamination. Plekha7 overexpression impedes the intrinsic and counteracts the Insm1-induced, NPC delamination. Our findings uncover a novel molecular mechanism underlying NPC delamination in which a BP-genic transcription factor specifically targets the integrity of the apical adherens junction belt, rather than adherens junction components as such. Tavano et al. identify a novel molecular mechanism underlying neural progenitor delamination from the ventricle, a prerequisite to form the subventricular zone, the germinal layer implicated in neocortex expansion. Downregulation of adherens-junction belt-specific protein Plekha7 is central to this mechanism.

Details

Original languageEnglish
Pages (from-to)1299-1314.e8
Number of pages16
JournalNeuron
Volume97
Issue number6
Publication statusPublished - 21 Mar 2018
Peer-reviewedYes

External IDs

PubMed 29503187

Keywords

ASJC Scopus subject areas

Keywords

  • AJ belt disassembly, basal progenitors, basal radial glia, Insm1, NPC delamination, Plekha7, subventricular zone

Library keywords