Neuregulin 1 growth factors regulate proliferation but not apoptosis of a CNS neuronal progenitor cell line

Growth factor-dependent proliferation of neuronal progenitors is an essential stage in CNS development. Although several of these growth factors have been identified, high levels of neuregulin 1 (NRG1) mRNA and protein expression in the CNS during the time of neuronal progenitor expansion suggest NRG1 growth factors may also play a key role in their proliferation. No previous studies have examined the expression of multiple NRG1 isoforms and receptors in these progenitors and their role in proliferation or apoptosis. Using a rat CNS clonal cell line with neuronal progenitor properties, we show for the first time these cells coexpress multiple NRG1 isoforms (NRGβ1, NRGβ3, CRD-NRGβ, and SMDF, but not GGF2 or any α isoforms) and all three cognate receptors (erbB2-4). We also show for the first time the presence of mRNA for all four variants of the erbB4 receptor in a single CNS cell type. Neutralizing antibody treatments suggest NRG1 isoforms and receptors are involved in proliferation but not apoptosis of these cells. This model system should be useful in future studies of the ligand specificity and function(s) of the erbB4 receptor variants.