Insulin-like growth factor-I (IGF-I), a 70-amino acid-protein structurally similar
to insulin, promotes cell proliferation and differentiation in multiple tissues. Most
of its effects are mediated by the Type I IGF receptor (IGF-IR), a heterotetramer
that has tyrosine kinase activity and phosphorylates insulin receptor substrates (IRS-1
and 2) which leads to the activation of two downstream signaling cascades: the MAP
kinase and the phosphatidylinositol 3-kinase (P3K) cascades. The growth-promoting
effects of IGF-I are prominent in the nervous system, qualifying this molecule as
a neurotrophin. Although the primary regulator of IGF-I expression is growth hormone
(GH), the developmental expression of IGF-I in various tissues precedes that of GH,
supporting an independent role of IGF-I in embryonic and fetal life [1]. This review
will examine the effect of IGF-I on central nervous system (CNS) development. The
specialized structure of the CNS is the product of a complex series of biological
events which result from the interaction between the cells' genetic program and environmental
influences. CNS development begins in the embryo with dorsal ectodermal cell proliferation
to form the neural plate, and, with its closure, the neural tube, followed by the
rapid division of pluripotential cells, their migration to the periphery of the neural
tube, and differentiation into neural or glial cells. During the latter stages, cells
form special structures such as nuclei, ganglia, cerebral cortical layers, and they
also develop a network with their cytoplasmic extensions, neurites. Many more cells
and connections are generated in fetal life than are found in the mature organism.
This excessive production of some cell groups and neurites may compensate for tissue
loss due to various injuries, and their selective elimination also constitutes an
efficient way to organize the architecture of the CNS. This elimination is believed
to be accomplished by apoptosis. The cells' intrinsic program for development includes
the expression of various genes at different times.Environmental influences, such
as extracellular matrix (ECM) molecules that attract or repel cells, afferent inputs,
and target-derived diffusible molecules modify and modulate cellular behavior. IGF-I
is among the molecules which affect several steps involved in development.
Key words
Insulin-Like Growth Factor - CNS
