| The neuregulin 1 (NRG1) growth factors arise from a single gene, have multiple isoforms produced by alternative splicing, and have three cognate receptors, erbB2, erbB3, and erbB4. They affect the proliferation, survival and differentiation of neural cells, and there is some evidence they can act in an autocrine manner in glial cells. More is known about their role in glial development, with very little information about effects on neuronal development.; The results of this study show the B104 CNS neuronal progenitor cell line and E13.5 rat spinal cord neuronal progenitors (NPs) both express mRNA and protein for multiple NRG1 ligands and receptors, and this expression is colocalized in both cell preparations. B104 cells do not express mRNA for glial growth factor 2 (GGF2) or any of the NRG alpha isoforms, whereas NPs do express mRNA for these isoforms. Additionally, GGF2, but not NRGα, protein is observed in NPs. In 8104 cells, NRGβ1, NRGβ3, and CRD-NRG are expressed throughout the cell body and processes, but CRD-NRG shows significantly weaker immunostaining in the processes. Immunoreactivity for the receptors is mainly localized to the cell body. A similar pattern is observed in E13.5 NPs, with additional GGF2 immunoreactivity mainly in the cell body.; Colocalization of the expression of NRGβ1 isoforms and each receptor in both B104 and E13.5 NPs, suggests the presence of an autocrine mechanism in these cells. Neutralizing antibodies in conjunction with a proliferation/apoptosis assay were used to determine the biological activity of NRG1 ligands and receptors and their role in an autocrine mechanism. Proliferation of B104 cells is reduced when cultured with anti-erbB2 and anti-panNRG1 but not with anti-erbB3 or anti-erbB4. None of the antibodies have any effect on the survival of B104 cells. Proliferation of E13.5 NP cells is not affected by any of the antibodies, however, apoptosis is dramatically decreased by anti-erbB3 but not anti-panNRG1. This suggests the presence of an unidentified ligand for erbB3. B104 cells may represent a different stage in the lineage of neuronal progenitors, since they respond to NRG1 differently (proliferation vs. apoptosis) and express NF-H (200 kDa), a more differentiated marker.; In addition to insight into the early events in neurogenesis, the data generated in this study may also have relevance to the regeneration or repair of the CNS. |
