Insm1 Induces Neural Progenitor Delamination in Developing Neocortex via Downregulation of the Adherens Junction Belt-Specific Protein Plekha7
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Pages (from-to) | 1299-1314.e8 |
Number of pages | 16 |
Journal | Neuron |
Volume | 97 |
Issue number | 6 |
Publication status | Published - 21 Mar 2018 |
Peer-reviewed | Yes |
External IDs
PubMed | 29503187 |
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Keywords
ASJC Scopus subject areas
Keywords
- AJ belt disassembly, basal progenitors, basal radial glia, Insm1, NPC delamination, Plekha7, subventricular zone