PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2

Shalaka Dhanraj Wahane, Nicole Hellbach, Mirja Tamara Prentzell, Stefan Christopher Weise, Riccardo Vezzali, Clemens Kreutz, Jens Timmer, Kerstin Krieglstein, Kathrin Thedieck, Tanja Vogel

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Development of the cerebral cortex is controlled by growth factors among which transforming growth factor beta (TGFβ) and insulin-like growth factor 1 (IGF1) have a central role. The TGFβ- and IGF1-pathways cross-talk and share signalling molecules, but in the central nervous system putative points of intersection remain unknown. We studied the biological effects and down-stream molecules of TGFβ and IGF1 in cells derived from the mouse cerebral cortex at two developmental time points, E13.5 and E16.5. IGF1 induces PI3K, AKT and the mammalian target of rapamycin complexes (mTORC1/mTORC2) primarily in E13.5-derived cells, resulting in proliferation, survival and neuronal differentiation, but has small impact on E16.5-derived cells. TGFβ has little effect at E13.5. It does not activate the PI3K- and mTOR-signalling network directly, but requires its activity to mediate neuronal differentiation specifically at E16.5. Our data indicate a central role of mTORC2 in survival, proliferation as well as neuronal differentiation of E16.5-derived cortical cells. mTORC2 promotes these cellular processes and is under control of PI3K-p110-alpha signalling. PI3K-p110-beta signalling activates mTORC2 in E16.5-derived cells but it does not influence cell survival, proliferation and differentiation. This finding indicates that different mTORC2 subtypes may be implicated in cortical development and that these subtypes are under control of different PI3K isoforms.

Original languageEnglish
Pages (from-to)255-267
Number of pages13
JournalJournal of Neurochemistry
Volume130
Issue number2
DOIs
StatePublished - Jul 2014
Externally publishedYes

Keywords

  • PI3K-isoform
  • PI3K-subunit
  • brain
  • cerebral cortex
  • insulin
  • neuron

Fingerprint

Dive into the research topics of 'PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2'. Together they form a unique fingerprint.

Cite this