Expanding the mind: insulin-like growth factor I and brain development

Endocrinology. 2008 Dec;149(12):5958-62. doi: 10.1210/en.2008-0920. Epub 2008 Aug 7.


Signaling through the type 1 IGF receptor (IGF1R) after interaction with IGF-I is crucial to the normal brain development. Manipulations of the mouse genome leading to changes in the expression of IGF-I or IGF1R significantly alters brain growth, such that IGF-I overexpression leads to brain overgrowth, whereas null mutations in either IGF-I or the IGF1R result in brain growth retardation. IGF-I signaling stimulates the proliferation, survival, and differentiation of each of the major neural lineages, neurons, oligodendrocytes, and astrocytes, as well as possibly influencing neural stem cells. During embryonic life, IGF-I stimulates neuron progenitor proliferation, whereas later it promotes neuron survival, neuritic outgrowth, and synaptogenesis. IGF-I also stimulates oligodendrocyte progenitor proliferation although inhibiting apoptosis in oligodendrocyte lineage cells and stimulating myelin production. These pleiotropic IGF-I activities indicate that other factors provide instructive signals for specific cellular events and that IGF-I acts to facilitate them. Studies of the few humans with IGF-I and/or IGF1R gene mutations indicate that IGF-I serves a similar role in man.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / growth & development
  • Brain / metabolism*
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / physiology
  • Models, Biological
  • Myelin Sheath / metabolism
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism
  • Oligodendroglia / physiology
  • Receptor, IGF Type 1 / metabolism*
  • Receptor, IGF Type 1 / physiology
  • Signal Transduction / physiology


  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1