mTOR regulates brain morphogenesis by mediating GSK3 signaling
Minhan Ka1, Gianluigi Condorelli2, James R Woodgett3
1Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Development (Cambridge, England)
|October 3, 2014
Summary
Mammalian target of rapamycin (mTOR) is essential for neural progenitor homeostasis and neuron production during brain development. Its interaction with glycogen synthase kinase 3 (GSK3) regulates progenitor pools and neuron generation.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Neural progenitor homeostasis is critical for brain development and neurological health.
- Mechanisms regulating neural progenitor maintenance and neuron production are not fully understood.
Purpose of the Study:
- To investigate the role of mammalian target of rapamycin (mTOR) in neural progenitor homeostasis.
- To elucidate the interplay between mTOR and glycogen synthase kinase 3 (GSK3) signaling in brain development.
Main Methods:
- Generated conditional mutant mice with mTOR deletion in neural progenitors and neurons.
- Utilized Nestin-cre and Nex-cre lines for targeted gene deletion.
- Analyzed cell cycle progression, progenitor self-renewal, and neuron production.
Main Results:
- mTOR deletion disrupted neural progenitor cell cycle progression and self-renewal.
- Neuron production was significantly suppressed following mTOR elimination.
- GSK3 was identified as an interacting partner of mTOR, regulating its activity in cortical progenitors.
- mTOR inactivation mitigated abnormal neural progenitor proliferation caused by GSK3 deletion.
Conclusions:
- The interaction between mTOR and GSK3 signaling is crucial for maintaining neural progenitor homeostasis during brain development.
- Dysregulation of this pathway contributes to neurological disorders.
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