Insulin-Like Growth Factor 1 Actions in Developing Brain and the Interaction with Wnt Pathway

ABSTRACT

Insulin like growth factor (IGF)-1 signaling through type 1 IGF receptor (IGF1R) is essential to the normal growth and development of the central nervous system. IGF-1 stimulates proliferation of neural stem cells and neural progenitors. IGF-1 also promotes survival and differentiation of neurons and oligodendrocytes, including neuritic outgrowth, synaptogenesis, and myelin production. The phosphatidylinositol 3 kinase (PI3)-Akt pathway and mitogen-activated protein (MAP) kinase pathway are two predominant mediators of IGF1-IGF1R signaling in neural cells. beta-catenin, a key molecule of the canonical Wnt signaling pathway, is also a downstream target of PI3-Akt-glycogen synthase kinase 3beta (GSK3beta) pathway. IGF-1 signaling through IGF1R interacts with canonical Wnt pathway at the levels of GSK3beta and beta-catenin rather than at the levels of Wnt ligands and Frizzled receptors to promote neural proliferation in developing central nervous system.