Pten deletion causes mTorc1-dependent ectopic neuroblast differentiation without causing uniform migration defects

Development. 2012 Sep;139(18):3422-31. doi: 10.1242/dev.083154. Epub 2012 Aug 8.

Abstract

Neuronal precursors, generated throughout life in the subventricular zone, migrate through the rostral migratory stream to the olfactory bulb where they differentiate into interneurons. We found that the PI3K-Akt-mTorc1 pathway is selectively inactivated in migrating neuroblasts in the subventricular zone and rostral migratory stream, and activated when these cells reach the olfactory bulb. Postnatal deletion of Pten caused aberrant activation of the PI3K-Akt-mTorc1 pathway and an enlarged subventricular zone and rostral migratory stream. This expansion was caused by premature termination of migration and differentiation of neuroblasts and was rescued by inhibition of mTorc1. This phenotype is reminiscent of lamination defects caused by Pten deletion in developing brain that were previously described as defective migration. However, live imaging in acute slices showed that Pten deletion did not cause a uniform defect in the mechanics of directional neuroblast migration. Instead, a subpopulation of Pten-null neuroblasts showed minimal movement and altered morphology associated with differentiation, whereas the remainder showed unimpeded directional migration towards the olfactory bulb. Therefore, migration defects of Pten-null neurons might be secondary to ectopic differentiation.

Publication types

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

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Electroporation
  • In Vitro Techniques
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Mice, Transgenic
  • Multiprotein Complexes
  • Neurons / cytology*
  • Neurons / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • TOR Serine-Threonine Kinases

Substances

  • Multiprotein Complexes
  • Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • Pten protein, mouse