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YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex

Kostic, M., Paridaen, J. T. M. L., Long, K. R., Kalebic, N., Langen, B., Gruebling, N., Wimberger, P., Kawasaki, H., Namba, T. & Huttner, W. B., 23-Apr-2019, In : Cell reports. 27, 4, p. 1103-1118.e6 22 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Milos Kostic
  • Judith T. M. L. Paridaen
  • Katherine R. Long
  • Nereo Kalebic
  • Barbara Langen
  • Nannette Gruebling
  • Pauline Wimberger
  • Hiroshi Kawasaki
  • Takashi Namba
  • Wieland B. Huttner

Neocortex expansion during mammalian evolution has been linked to an increase in proliferation of basal progenitors in the subventricular zone. Here, we explored a potential role of YAP, the major down-stream effector of the Hippo pathway, in proliferation of basal progenitors. YAP expression and activity are high in ferret and human basal progenitors, which exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. Conditional expression of a constitutively active YAP in mouse basal progenitors resulted in increased proliferation of basal progenitor and promoted production of upper-layer neurons. Pharmacological and genetic interference with YAP function in ferret and human developing neocortex resulted in decreased abundance of cycling basal progenitors. Together, our data indicate that YAP is necessary and sufficient to promote the proliferation of basal progenitors and suggest that increases in YAP levels and presumably activity contributed to the evolutionary expansion of the neocortex.

Original languageEnglish
Pages (from-to)1103-1118.e6
Number of pages22
JournalCell reports
Volume27
Issue number4
Publication statusPublished - 23-Apr-2019

    Keywords

  • OUTER SUBVENTRICULAR ZONE, RADIAL GLIA, EXTRACELLULAR-MATRIX, GENE-EXPRESSION, HIPPO PATHWAY, NEURONS ARISE, SELF-RENEWAL, CELL CONTACT, SIZE-CONTROL, ORGAN SIZE

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