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

Tavano, S., Taverna, E., Kalebic, N., Haffner, C., Namba, T., Dahl, A., Wilsch-Braeuninger, M., Paridaen, J. T. M. L. & Huttner, W. B., 21-Mar-2018, In : Neuron. 97, 6, p. 1299-1344 25 p.

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

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DOI

  • Stefania Tavano
  • Elena Taverna
  • Nereo Kalebic
  • Christiane Haffner
  • Takashi Namba
  • Andreas Dahl
  • Michaela Wilsch-Braeuninger
  • Judith T. M. L. Paridaen
  • Wieland B. Huttner

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 mechanismby 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.

Original languageEnglish
Pages (from-to)1299-1344
Number of pages25
JournalNeuron
Volume97
Issue number6
Publication statusPublished - 21-Mar-2018

    Keywords

  • PRIMARY CILIUM, CELL BIOLOGY, RADIAL GLIA, STEM-CELLS, EVOLUTION, NEUROGENESIS, EXPANSION, PROMOTES, AJUBA, MAINTENANCE

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