Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neuron. 2010 Apr 15;66(1):69-84. doi: 10.1016/j.neuron.2010.03.019.

The apical complex couples cell fate and cell survival to cerebral cortical development.

Author information

  • 1Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Division of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

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.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID:
20399730
[PubMed - indexed for MEDLINE]
PMCID:
PMC2872122
Free PMC Article

Images from this publication.See all images (8)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk