Pten coordinates retinal neurogenesis by regulating Notch signalling

EMBO J. 2012 Feb 15;31(4):817-28. doi: 10.1038/emboj.2011.443. Epub 2011 Dec 6.

Abstract

Development of nervous tissue is a coordinated process of neural progenitor cell (NPC) proliferation and neuronal differentiation. Intracellular signalling events that regulate the balance between NPC proliferation and neuronal differentiation, therefore, determine the size and composition of nervous tissues. Here, we demonstrate that negative regulation of phosphoinosite 3-kinase (PI3K)-Akt signalling by phosphatase tensin homologue (Pten) is essential for maintaining NPC population in mouse retina. We found that mouse retinal progenitor cells (RPCs) lacking the Pten gene complete neurogenesis earlier than their normal developmental schedule, resulting in their premature depletion in the mature retina. We further discover that Notch intracellular domain (NICD) fails to form transcription activator complex in Pten-deficient RPCs, and thereby unable to support RPC maintenance. Taken together, our results suggest that Pten plays a pivotal role in retinal neurogenesis by supporting Notch-driven RPC maintenance against neurogenic PI3K-Akt signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Neurogenesis / physiology*
  • Neurons / cytology*
  • Neurons / metabolism
  • PTEN Phosphohydrolase / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Notch / metabolism*
  • Retina / cytology*
  • Signal Transduction*
  • Transcription, Genetic

Substances

  • Receptors, Notch
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, mouse