ArticleCerebral cortex (New York, N.Y. : 1991)2014
Fetal brain mTOR signaling activation in tuberous sclerosis complex.
Article in Cerebral cortex (New York, N.Y. : 1991), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 112 citations in OpenAlex.
- Spatially Organized IGF1-mTOR Signaling Controls Human Forebrain Progenitor F ate Through Coordinated Transcriptional and Translational Programs.bioRxiv : the preprint server for biology · 2025Article
- Insights into Tuberous Sclerosis Complex : From Genes to Clinics.Journal of Korean Neurosurgical Society · 2025Article
- Altered cortical excitability in tuberous sclerosis and the effect of mTOR inhibitors: An intracranial electrical stimulation study.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2025Article
- Focal postnatal deletion ofFrontiers in molecular neuroscience · 2025Article
- The role of SGK1 in neurologic diseases: A friend or foe?IBRO neuroscience reports · 2024Review
- Balloon cells in malformations of cortical development: friends or foes?Acta epileptologica · 2024Review
- Seizure reduction in TSC2-mutant mouse model by an mTOR catalytic inhibitor.Annals of clinical and translational neurology · 2023Article
- Altered functional connectivity and network excitability in a model of cortical dysplasia.Scientific reports · 2023Article
- Epilepsy Severity Is Associated With Head Circumference and Growth Rate in Infants With Tuberous Sclerosis Complex.Pediatric neurology · 2023Observational
- Modeling genetic mosaicism of the mammalian target of rapamycin pathway in the cerebral cortex.Frontiers in mammal science · 2023Article
- Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.Immunity, inflammation and disease · 2022Article
- Article
- Hypomyelinating Leukodystrophy 8 (HLD8)-Associated Mutation of POLR3B Leads to Defective Oligodendroglial Morphological Differentiation Whose Effect Is Reversed by Ibuprofen.Neurology international · 2022Article
- Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period.Journal of neurodevelopmental disorders · 2022Article
- SGK1, a Critical Regulator of Immune Modulation and Fibrosis and a Potential Therapeutic Target in Chronic Graft-Versus-Host Disease.Frontiers in immunology · 2022Review
- Hypomyelinating Leukodystrophy 7 (HLD7)-Associated Mutation of POLR3A Is Related to Defective Oligodendroglial Cell Differentiation, Which Is Ameliorated by Ibuprofen.Neurology international · 2021Article
- Corrigendum: Convergent and Divergent Mechanisms of Epileptogenesis in mTORopathies.Frontiers in neuroanatomy · 2021Article
- Convergent and Divergent Mechanisms of Epileptogenesis in mTORopathies.Frontiers in neuroanatomy · 2021Review
- Dynamic analysis of 4E-BP1 phosphorylation in neurons with Tsc2 or Depdc5 knockout.Experimental neurology · 2020Article
- The Neurodevelopmental Pathogenesis of Tuberous Sclerosis Complex (TSC).Frontiers in neuroanatomy · 2020Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Tuberous sclerosis complex (TSC) is characterized by developmental malformations of the cerebral cortex known as tubers, comprised of cells that exhibit enhanced mammalian target of rapamycin (mTOR) signaling. To date, there are no reports of mTORC1 and mTORC2 activation in fetal tubers or in neural progenitor cells lacking Tsc2. We demonstrate mTORC1 activation by immunohistochemical detection of substrates phospho-p70S6K1 (T389) and phospho-S6 (S235/236), and mTORC2 activation by substrates phospho-PKCα (S657), phospho-Akt (Ser473), and phospho-SGK1 (S422) in fetal tubers. Then, we show that Tsc2 shRNA knockdown (KD) in mouse neural progenitor cells (mNPCs) in vitro results in enhanced mTORC1 (phospho-S6, phospho-4E-BP1) and mTORC2 (phospho-Akt and phospho-NDRG1) signaling, as well as a doubling of cell size that is rescued by rapamycin, an mTORC1 inhibitor. Tsc2 KD in vivo in the fetal mouse brain by in utero electroporation causes disorganized cortical lamination and increased cell volume that is prevented with rapamycin. We demonstrate for the first time that mTORC1 and mTORC2 signaling is activated in fetal tubers and in mNPCs following Tsc2 KD. These results suggest that inhibition of mTOR pathway signaling during embryogenesis could prevent abnormal brain development in TSC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.