Neuronal and glial expression of heparin-binding EGF-like growth factor in central nervous system of prenatal and early postnatal rat

We investigated heparin-binding epidermal growth factor-like growth factor (HB-EGF) gene and protein expression in the central nervous system of prenatal and early postnatal rats. Assay by northern blot analysis showed that the HB-EGF mRNA was markedly expressed in the brain. In situ hybridization and immunohistochemical techniques showed that concordant expression of HB-EGF mRNA and protein was widely observed in the neurons and interfascicular oligodendrocytes, especially in the cerebellum, the hippocampus, the cerebral cortex, the subventricular area, and the brain stem nuclei. The intense expression of the HB-EGF mRNA was related anatomically and temporally to the proliferating neuroblasts in the external granular layer of the cerebellum and the subventricular layer of the cerebrum. These findings suggest that HB-EGF acts as a mitogen for the neuroblasts. Moreover, HB-EGF expression was observed in the post-mitogenic cells, such as in the cells of the molecular layer, the white matter, the IGL, or the Purkinje cells of the cerebellum. Since EGF receptors are abundantly expressed in the post-mitogenic period, the HB-EGF mRNA expression observed in the post- mitogenic period in our study suggests that HB-EGF also has a non-mitogenic function. These results suggest that HB-EGF significantly contributes to the development of the brain.