p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex

Camille Belzil, Naoyuki Asada, Kei Ichiro Ishiguro, Takeo Nakaya, Kari Parsons, Valentina Pendolino, Gernot Neumayer, Marina Mapelli, Yoshihiro Nakatani, Kamon Sanada, Minh Dang Nguyen

Research output: Contribution to journalArticle

Abstract

Apical neural progenitors (aNPs) drive neurogenesis by means of a program consisting of self-proliferative and neurogenic divisions. The balance between these two manners of division sustains the pool of apical progenitors into late neurogenesis, thereby ensuring their availability to populate the brain with terminal cell types. Using knockout and in utero electroporation mouse models, we report a key role for the microtubule-associated protein 600 (p600) in the regulation of spindle orientation in aNPs, a cellular event that has been associated with cell fate and neurogenesis. We find that p600 interacts directly with the neurogenic protein Ndel1 and that aNPs knockout for p600, depleted of p600 by shRNA or expressing a Ndel1-binding p600 fragment all display randomized spindle orientation. Depletion of p600 by shRNA or expression of the Ndel1-binding p600 fragment also results in a decreased number of Pax6-positive aNPs and an increased number of Tbr2-positive basal progenitors destined to become neurons. These Pax6-positive aNPs display a tilted mitotic spindle. In mice wherein p600 is ablated in progenitors, the production of neurons is significantly impaired and this defect is associated with microcephaly. We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis.

Original languageEnglish
Pages (from-to)475-485
Number of pages11
JournalBiology Open
Volume3
Issue number6
DOIs
Publication statusPublished - Jun 15 2014

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Keywords

  • Apical neural progenitors
  • Ndel1
  • Neurogenesis
  • P600
  • Spindle orientation
  • UBR4

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Belzil, C., Asada, N., Ishiguro, K. I., Nakaya, T., Parsons, K., Pendolino, V., Neumayer, G., Mapelli, M., Nakatani, Y., Sanada, K., & Nguyen, M. D. (2014). p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex. Biology Open, 3(6), 475-485. https://doi.org/10.1242/bio.20147807