Gene interactions and pathways from curated databases and text-mining
Cell stem cell 2011, PMID: 22056141

Sustained activation of mTOR pathway in embryonic neural stem cells leads to development of tuberous sclerosis complex-associated lesions.

Magri, Laura; Cambiaghi, Marco; Cominelli, Manuela; Alfaro-Cervello, Clara; Cursi, Marco; Pala, Mauro; Bulfone, Alessandro; Garc├Ča-Verdugo, Jose Manuel; Leocani, Letizia; Minicucci, Fabio; Poliani, Pietro Luigi; Galli, Rossella

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by hamartomatous neurological lesions that exhibit abnormal cell proliferation and differentiation. Hyperactivation of mTOR pathway by mutations in either the Tsc1 or Tsc2 gene underlies TSC pathogenesis, but involvement of specific neural cell populations in the formation of TSC-associated neurological lesions remains unclear. We deleted Tsc1 in Emx1-expressing embryonic telencephalic neural stem cells (NSCs) and found that mutant mice faithfully recapitulated TSC neuropathological lesions, such as cortical lamination defects and subependymal nodules (SENs). These alterations were caused by enhanced generation of SVZ neural progeny, followed by their premature differentiation and impaired maturation during both embryonic and postnatal development. Notably, mTORC1-dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs. Thus, finely tuned mTOR activation in embryonic NSCs may be critical to prevent development of TSC-associated brain lesions.

Diseases/Pathways annotated by Medline MESH: Epilepsy, Macrocephaly, Tuberous Sclerosis
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Text Mining Data

Akt ⊣ mTORC1: " Notably, mTORC1 dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs "

STAT3 → mTORC1: " Notably, mTORC1 dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs "

Manually curated Databases

No curated data.