INSULIN-LIKE GROWTH-FACTOR II EXPRESSION IN THE DEVELOPING HUMAN BRAIN

Insulin-like growth factor II (IGF-II) is a polypeptide hormone with insulin-like metabolic activity and neurotrophic activity in vitro that has been implicated in human brain development. In this study, we used northern blot analysis to examine the patterns of IGF-II mRNA expression in selected regions of 18 human brains from cases ranging in age from 20 gestational weeks to 2.5 years (median age 31 gestational weeks). The expression of IGF-II mRNA was widespread throughout the brain from midgestation through the perinatal period. Each region showed a distinct developmental pattern of expression and IGF-II mRNA levels varied considerably between regions. The highest levels of expression at all ages were in leptomeninges and choroid plexus. After two postnatal months, IGF-II mRNA virtually disappeared from parenchymal regions. Beyond the perinatal period, IGF-II expression persisted primarily in choroid plexus. Transcripts of both 6.0 and 4.8 kb were detected in most brain regions. A developmental change in the relative amounts of the two transcripts occurred in choroid plexus, leptomeninges and medulla. The expression of IGF-II mRNA in the brain parenchyma during the last half of gestation correlates with a period of major brain growth and supports the hypothesis that high levels of IGF-II stimulate the proliferation and differentiation of neural cells early in development.