Back to Search
Start Over
The apical complex couples cell fate and cell survival to cerebral cortical development.
- Source :
-
Neuron [Neuron] 2010 Apr 15; Vol. 66 (1), pp. 69-84. - Publication Year :
- 2010
-
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.<br /> (Copyright 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Differentiation genetics
Cell Survival genetics
Cerebral Cortex cytology
Cerebral Cortex growth & development
Gene Expression Regulation, Developmental physiology
Gene Targeting
Intracellular Signaling Peptides and Proteins metabolism
Membrane Proteins
Mice
Mice, Transgenic
Neurogenesis genetics
Neurons metabolism
Nucleoside-Phosphate Kinase
Organogenesis genetics
Organogenesis physiology
Protein Serine-Threonine Kinases metabolism
Signal Transduction genetics
TOR Serine-Threonine Kinases
Cell Differentiation physiology
Cerebral Cortex metabolism
Neurogenesis physiology
Neurons cytology
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 66
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 20399730
- Full Text :
- https://doi.org/10.1016/j.neuron.2010.03.019