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Journal of Neuroscience, Vol 13, 5092-5104, Copyright © 1993 by Society for Neuroscience
Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I gene expression during brain development
C Bondy and WH Lee
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Maryland 20892.
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) potently
modulate the interactions of IGF-I and -II with the IGF-I receptor.
Previous studies have shown that IGFBP2 gene expression is localized in
astroglia, where it is anatomically and temporally coordinated with
neuronal IGF-I expression during postnatal brain development. The present
study shows that IGFBP5 gene expression is also highly abundant during
brain development and also demonstrates significant spatiotemporal
correlation with IGF-I, but exhibits a neuroanatomical distribution that is
entirely distinct from IGFBP2. IGFBP5 and IGF-I mRNAs are synchronously
coexpressed in principal neurons of sensory relay systems, including the
olfactory bulb, medial and dorsal lateral geniculate bodies, and ventral
tier, cochlear, lemniscal, and vestibular nuclei. They are also transiently
coexpressed in principal neurons of the anterodorsal nucleus, but IGF-I
mRNA disappears from this structure shortly after birth, while IGFBP5 mRNA
remains highly abundant here in the adult. IGFBP5 and IGF-I gene expression
demonstrate a temporally coordinated laminar association in the developing
cerebellar cortex and hippocampal formation. IGF-I mRNA is concentrated in
Purkinje cells, while IGFBP5 mRNA is localized in the external germinal
zone in the developing cerebellar cortex. IGFBP5 mRNA is transiently
expressed in the retrosplenial and cingulate cortex, subiculum, Ammon's
horn, and amygdala, while IGF-I mRNA is contemporaneously localized in
large interneurons distributed throughout the hippocampal formation. IGFBP5
mRNA is localized in the lateral ventricular germinal zone at birth and
remains in the subventricular zone into maturity. It is also detected in
forebrain white matter tracts and olfactory nerve from the second week
after birth into maturity. Thus IGFBP5, in addition to IGFBP2, may be a
significant determinant of IGF action in the brain. Colocalization in some
sites and paralocalization with IGF-I in other sites suggests the potential
for autocrine and paracrine interaction between the binding protein and
IGF-I in different settings. Arguments are advanced suggesting a role for
IGFBPs in the targeting of IGF action to specific cell addresses during
brain development.
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