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Insm1 induces neural progenitor delamination in developing neocortex via down-regulation of the adherens junction belt-specific protein Plekha7

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.

ORGANISM(S): Mus musculus

PROVIDER: GSE109709 | GEO | 2018/02/15

REPOSITORIES: GEO

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Insm1 induces neural progenitor delamination in developing neocortex via down-regulation of the adherens junction belt-specific protein Plekha7

Project description:Insm1 induces neural progenitor delamination in developing neocortex via down-regulation of the adherens junction belt-specific protein Plekha7

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2009-12-14 | E-GEOD-19299 | biostudies-arrayexpress

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HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1

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The role of Insulinoma associated 1 protein in the development of the mammalian neocortex

Project description:Basal (intermediate) progenitors are the major source of neurons in the mammalian cerebral cortex. The molecular machinery governing basal progenitor biogenesis is unknown. Here we show that the zinc finger transcription factor Insm1 (insulinoma-associated 1) is expressed specifically in progenitors undergoing neurogenic divisions and has a key role in basal progenitor formation. Mouse embryos lacking Insm1 contained half the number of basal progenitors and showed a marked reduction in cortical plate radial thickness. Forced premature expression of Insm1 in neuroepithelial cells resulted in their mitosis occurring at the basal (rather than apical) side of the ventricular zone and induced expression of the basal progenitor marker Tbr2. Remarkably, these cells remained negative for Tis21, a marker of neurogenic progenitors, and did not generate neurons but underwent self-amplification. Our data imply that Insm1 is involved in the generation and expansion of basal progenitors, a hallmark of cerebral cortex evolution. Keywords: knock out, genetic modification,

2008-10-14 | GSE12294 | GEO

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