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Abstract
BackgroundIGFBP-4 has been considered as a factor involving in development of the central nervous system (CNS), but its role needs to be further clarified. In present study, the localization of IGFBP-4 expression in the embryonic forebrain, midbrain and hindbrain was determined using immunohistochemistry, and the levels of IGFBP-4 protein and mRNA were semi-quantified using RT-PCR and Western blot in the embryonic (forebrain, midbrain and hindbrain) and postnatal brain (cerebral cortex, cerebellum and midbrain).ResultsA clear immunoreactivity of IGFBP-4 covered almost the entire embryonic brain (forebrain, midbrain, hindbrain) from E10.5 to E18.5, except for the area near the ventricle from E14.5. The change of IGFBP-4 mRNA level was regularly from E10.5 to E18.5: its expression peaked at E13.5 and E14.5, followed by gradual decreasing from E15.5. The expression of IGFBP-4 protein was similar to that of mRNA in embryonic stage. After birth, the pattern of IGFBP-4 expression was shown to be rather divergent in different brain areas. In the cerebral cortex, the IGFBP-4 mRNA increased gradually after birth (P0), while the protein showed little changes from P0 to P28, but decreased significantly at P70. In the cerebellum, the IGFBP-4 mRNA decreased gradually from P0, reached the lowest level at P21, and then increased again. However, its protein level gradually increased from P0 to P70. In the midbrain, the IGFBP-4 mRNA first decreased and reached its lowest level at P28 before it increased, while the protein remained constant from P0 to P70. At P7, P14, P21, P28 and P70, the levels of IGFBP-4 mRNA in the cerebral cortex were significantly higher than that in the cerebellum or in the midbrain. Differently, the protein levels in the cerebellum were significantly higher than that either in the cerebral cortex or in the midbrain at P14, P21, P28 and P70.ConclusionsThe temporal expression pattern of IGFBP-4 in the embryonic brain from E10.5 to E18.5 was consistent with the course of neurogenesis in the ventricular zone, suggesting an important role of IGFBP-4 in regulating differentiation of neural stem cells. A strikingly higher abundance of the IGFBP-4 protein observed in the cerebellum from P14 to P70 suggests that IGFBP-4 may participate in the maintenance of cerebellar plasticity.
Highlights
insulin-like growth factor binding protein-4 (IGFBP-4) has been considered as a factor involving in development of the central nervous system (CNS), but its role needs to be further clarified
Among the large number of differential genes identified as important factors for regulating brain development at certain stages, we have found that the gene for insulin-like growth factor binding protein-4 (IGFBP-4) is expressed more highly in mature neurons than in neural precursors, indicating that IGFBP-4 may potentially act as a proneuronal differentiation factor [2]
It is already known that IGFBP-4 is one member of the IGFBP family, which is mainly composed of six highly homologous proteins that bind insulin-like growth factors (IGFs) with high affinity to regulate its activity [3]
Summary
IGFBP-4 has been considered as a factor involving in development of the central nervous system (CNS), but its role needs to be further clarified. Since the CNS is composed of millions of distinct neural cells, its complex and accurate functions must depend on the highly organized architecture of the cells that assemble in precise circuits. Among the large number of differential genes identified as important factors for regulating brain development at certain stages, we have found that the gene for insulin-like growth factor binding protein-4 (IGFBP-4) is expressed more highly in mature neurons than in neural precursors, indicating that IGFBP-4 may potentially act as a proneuronal differentiation factor [2]. The physiological significance of the glycosylation in IGFBP-4 is unknown
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