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

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

A Joseph D'Ercole  1 , Ping Ye
Affiliations
Review

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

A Joseph D'Ercole et al. Endocrinology. 2008 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1
Alternative models of IGF1R signaling in neural progenitors. A, IGF1R signaling asymmetric division of NSC. B, IGF1R stimulation of radial glia proliferation leading to a replicate radial glial cell and a neuron progenitor. In this model, radial glia also give rise to astroglia and oligodendrocyte, albeit at a later time in development. IZ, Intermediate zone.
Figure 2
Figure 2
Representative photomicrographs of PLP mRNA in situ hybridization of corpus callosum (CC) and myelin basic protein (MBP) immunocytochemical staining (ICC) of brainstem in 6-wk-old IGF1Roligo-KO mice and their littermate controls. CTX, Cerebral cortex. Note that the number of PLP mRNA-expressing oligodendrocytes and the amount of myelin basic protein are much less in the IGF1Roligo-KO mice.
See this image and copyright information in PMC

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