Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis

Life Sci Alliance. 2019 Mar 25;2(2):e201800218. doi: 10.26508/lsa.201800218. Print 2019 Apr.


Neural stem/progenitor cells (NSPCs) of the ventricular-subventricular zone (V-SVZ) are candidate cells of origin for many brain tumors. However, whether NSPCs in different locations within the V-SVZ differ in susceptibility to tumorigenic mutations is unknown. Here, single-cell measurements of signal transduction intermediates in the mechanistic target of rapamycin complex 1 (mTORC1) pathway reveal that ventral NSPCs have higher levels of signaling than dorsal NSPCs. These features are linked with differences in mTORC1-driven disease severity: introduction of a pathognomonic Tsc2 mutation only results in formation of tumor-like masses from the ventral V-SVZ. We propose a direct link between location-dependent intrinsic growth properties imbued by mTORC1 and predisposition to tumor development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Animals
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology*
  • Carcinogenesis / metabolism*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Disease Susceptibility / metabolism
  • Female
  • Humans
  • Lateral Ventricles / cytology*
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / metabolism*
  • Signal Transduction
  • Thyroid Nuclear Factor 1 / metabolism
  • Tuberous Sclerosis / pathology*


  • NKX2-1 protein, human
  • Thyroid Nuclear Factor 1
  • Mechanistic Target of Rapamycin Complex 1