ArticleDisease models & mechanisms2013
Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models.
Article in Disease models & mechanisms, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Developmental mechanisms underlying pediatric epilepsy.Frontiers in neurology · 2025Review
- Premature cognitive decline in a mouse model of tuberous sclerosis.Aging cell · 2024Article
- Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2023Review
- Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model.The Journal of clinical investigation · 2023Article
- Synaptic hyperexcitability of cytomegalic pyramidal neurons contributes to epileptogenesis in tuberous sclerosis complex.Cell reports · 2022Article
- Abnormal activation of Yap/Taz contributes to the pathogenesis of tuberous sclerosis complex.Human molecular genetics · 2022Article
- Hyperactivation of mTORC1 in a double hit mutant zebrafish model of tuberous sclerosis complex causes increased seizure susceptibility and neurodevelopmental abnormalities.Frontiers in cell and developmental biology · 2022Article
- Mechanistic target of rapamycin signaling in human nervous system development and disease.Frontiers in molecular neuroscience · 2022Review
- Effects of Mutations in TSC Genes on Neurodevelopment and Synaptic Transmission.International journal of molecular sciences · 2021Review
- Article
- Single-cell RNA-seq analysis revealed long-lasting adverse effects of tamoxifen on neurogenesis in prenatal and adult brains.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tuberous Sclerosis Complex as Disease Model for Investigating mTOR-Related Gliopathy During Epileptogenesis.Frontiers in neurology · 2020Review
- The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex.Journal of neurodevelopmental disorders · 2019Review
- Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis.Life science alliance · 2019Article
- Role of mTOR Complexes in Neurogenesis.International journal of molecular sciences · 2018Review
- mTOR Signaling and Neural Stem Cells: The Tuberous Sclerosis Complex Model.International journal of molecular sciences · 2018Review
- Tuberous sclerosis complex-associated CNS abnormalities depend on hyperactivation of mTORC1 and Akt.The Journal of clinical investigation · 2018Article
- Loss of skills and onset patterns in neurodevelopmental disorders: Understanding the neurobiological mechanisms.Autism research : official journal of the International Society for Autism Research · 2018Review
- Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias.Cell reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, and is caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations - such as intractable epilepsy, mental retardation and autism - that are intimately associated with peculiar CNS lesions known as cortical tubers (CTs). The existence of a significant genotype-phenotype correlation in individuals bearing mutations in either TSC1 or TSC2 is highly controversial. Similar to observations in humans, mouse modeling has suggested that a more severe phenotype is associated with mutation in Tsc2 rather than in Tsc1. However, in these mutant mice, deletion of either gene was achieved in differentiated astrocytes. Here, we report that loss of Tsc1 expression in undifferentiated radial glia cells (RGCs) early during development yields the same phenotype detected upon deletion of Tsc2 in the same cells. Indeed, the same aberrations in cortical cytoarchitecture, hippocampal disturbances and spontaneous epilepsy that have been detected in RGC-targeted Tsc2 mutants were observed in RGC-targeted Tsc1 mutant mice. Remarkably, thorough characterization of RGC-targeted Tsc1 mutants also highlighted subventricular zone (SVZ) disturbances as well as STAT3-dependent and -independent developmental-stage-specific defects in the differentiation potential of ex-vivo-derived embryonic and postnatal neural stem cells (NSCs). As such, deletion of either Tsc1 or Tsc2 induces mostly overlapping phenotypic neuropathological features when performed early during neurogenesis, thus suggesting that the timing of mTOR activation is a key event in proper neural development.
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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.