The Apical Complex Couples Cell Fate and Cell Survival to Cerebral Cortical Development

Seonhee Kim, Maria K. Lehtinen, Alessandro Sessa, Mauro W. Zappaterra, Seo Hee Cho, Dilenny Gonzalez, Brigid Boggan, Christina A. Austin, Jan Wijnholds, Michael J. Gambello, Jarema Malicki, Anthony S. LaMantia, Vania Broccoli, Christopher A. Walsh

Research output: Contribution to journalArticle

Abstract

Cortical development depends upon tightly controlled cell fate and cell survival decisions that generate a functional neuronal population, but the coordination of these two processes is poorly understood. Here we show that conditional removal of a key apical complex protein, Pals1, causes premature withdrawal from the cell cycle, inducing excessive generation of early-born postmitotic neurons followed by surprisingly massive and rapid cell death, leading to the abrogation of virtually the entire cortical structure. Pals1 loss shows exquisite dosage sensitivity, so that heterozygote mutants show an intermediate phenotype on cell fate and cell death. Loss of Pals1 blocks essential cell survival signals, including the mammalian target of rapamycin (mTOR) pathway, while mTORC1 activation partially rescues Pals1 deficiency. These data highlight unexpected roles of the apical complex protein Pals1 in cell survival through interactions with mTOR signaling.

Original languageEnglish
Pages (from-to)69-84
Number of pages16
JournalNeuron
Volume66
Issue number1
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Devbio
  • Molneuro

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kim, S., Lehtinen, M. K., Sessa, A., Zappaterra, M. W., Cho, S. H., Gonzalez, D., Boggan, B., Austin, C. A., Wijnholds, J., Gambello, M. J., Malicki, J., LaMantia, A. S., Broccoli, V., & Walsh, C. A. (2010). The Apical Complex Couples Cell Fate and Cell Survival to Cerebral Cortical Development. Neuron, 66(1), 69-84. https://doi.org/10.1016/j.neuron.2010.03.019