Caveat mTOR: aberrant signaling disrupts corticogenesis
1Department of Medicine and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. lucy.osborne@utoronto.ca
The Journal of Clinical Investigation
|April 29, 2010
Summary
Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is linked to mTOR pathway activation. Reduced STRADalpha causes PMSE-like defects, suggesting mTOR inhibitors like rapamycin as potential therapies.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- The mammalian target of rapamycin (mTOR) pathway is implicated in various brain malformations.
- Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a severe neurological disorder.
Purpose of the Study:
- To investigate the role of STRADalpha in PMSE pathogenesis.
- To determine the link between STRADalpha deficiency and mTOR signaling in PMSE.
Main Methods:
- Studied the effects of STRADalpha reduction during mouse corticogenesis.
- Analyzed cellular phenotypes and neuronal migration in vivo.
Main Results:
- Reduced STRADalpha levels caused cellular defects and neuronal migration issues mirroring PMSE.
- Demonstrated activation of mTOR signaling in the context of STRADalpha deficiency.
Conclusions:
- STRADalpha is crucial for cell polarity and growth during corticogenesis.
- mTOR pathway activation is a key feature of PMSE.
- Rapamycin may offer a therapeutic strategy for PMSE.
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