Localization of insulin-like growth factor binding protein-2 messenger RNA during postnatal brain development: Correlation with insulin-like growth factors I and II

Abstract

Insulin-like growth factor binding protein-2 binds insulin-like growth factors I and II with high affinity and modulates the interaction of these ligands with the type I insulin-like growth factor receptor. Previously we have shown that insulin-like growth factor binding protein-2 and insulin-like growth factor-I gene expression are spatiotemporally co-ordinated in the developing retina and cerebellum. The present study examined other brain regions and found a similar correlation in insulin-like growth factor binding protein-2 and insulin-like growth factor-I gene expression in relay stations of developing sensory and cerebellar networks of the rat. In these sites, as in the cerebellum and retina, insulin-like growth factor-I messenger RNA is localized in the principal or projection neurons and insulin-like growth factor binding protein-2 messenger RNA is localized in surrounding astroglia. Outside these sensory relay centers, the relationship of insulin-like growth factor binding protein-2 to insulin-like growth factor-I gene expression is not so well defined. In the hippocampal formation, insulin-like growth factor-I messenger RNA is present in large interneurons and insulin-like growth factor binding protein-2 messenger RNA in regional astrocytes; their timing is co-ordinated, with peak levels seen about postnatal day 12, but their anatomical association is not apparent. The least degree of correlation between local insulin-like growth factor-I and insulin-like growth factor binding protein-2 gene expression is found in the neocortex, where insulin-like growth factor-I is abundant in scattered large neurons from postnatal days 3 to 20. In contrast, insulin-like growth factor binding protein-2 messenger RNA is widely expressed throughout the neocortex from before birth to about postnatal day 12, in a pattern consistent with expression by nascent astroglia. Insulin-like growth factor binding protein-2 gene expression is greatly reduced throughout the brain by the third week after birth; in response to optic nerve transection, however, there is a resurgence of gene expression for this factor by activated astrocytes in affected retinal target regions. Insulin-like growth factor binding protein-2 and insulin-like growth factor-II messenger RNAs are co-localized in the choroid plexus and leptomeninges from the time of birth onward without diminution. In summary, insulin-like growth factor binding protein-2 demonstrates complex patterns of gene expression during postnatal brain development—some of which appear to be closely related to local insulin-like growth factor synthesis and some of which appear independent of it. The spatiotemporal correlation between astroglial insulin-like growth factor binding protein-2 and neuronal insulin-like growth factor-I expression is restricted to maturing sensory and cerebellar projection systems, suggesting a system-specific function for insulin-like growth factor-I and insulin-like growth factor binding protein-2 interaction in the differentiation of these centers.