The four isoforms of the tyrosine kinase receptor ErbB4 provide neural progenitor cells with an adhesion preference for the transmembrane type III isoform of the ligand neuregulin 1.

Soluble and transmembrane neuregulin 1 isoforms can act as short-range and long-range attractants for migration of cortical and olfactory interneurons expressing ErbB4, a tyrosine kinase receptor whose characteristics are strongly affected by alternative splicing. Here, we have investigated the expression of the four ErbB4 isoforms and we found that all of them are expressed by neural progenitor cells migrating from the subventricular zone toward the olfactory bulb through the rostral migratory stream. We quantified the absolute expression of the different ErbB4 isoforms and found that all of them are highly expressed in the regions characterized by high interneuron migration, whereas in the olfactory bulb regions, where migration stops, ErbB4 isoforms containing exon JMb and lacking exon cyt1 (called 'cyt2 isoforms') are expressed more than isoforms containing exons JMa and cyt1. Indeed, we have shown previously that neural progenitor cells stably expressing ErbB4-JMb-cyt2 have a very low migratory activity. To investigate whether the different ErbB4 isoforms confer a distinct adhesion preference for transmembrane neuregulin 1, neural progenitor cells expressing these were tested in vitro in the stripe choice assay. We found that each of the four ErbB4 isoforms is able to confer cells with an adhesion preference for cells expressing the transmembrane neuregulin 1 type III.

Morphological and biomolecular characterization of the neonatal olfactory bulb ensheathing cell line.

Cell transplantation therapy has raised a great interest in the perspective of its employment for nerve tissue repair. Among the various cell populations proposed, olfactory ensheathing glial cells have raised great interest over recent years, especially in the perspective of their employment for neural repair because of their homing capacity in both central and peripheral nervous system. This paper is aimed to provide an in vitro characterization of the NOBEC (neonatal olfactory bulb ensheathing cell) line that was obtained from primary cells dissociated from rat neonatal olfactory bulb (OB) and immortalized by retroviral transduction of SV40 large T antigen. Light and electron microscopy investigation showed that NOBECs are a homogeneous cell population both at structural and ultrastructural level. RT-PCR, Western blotting and immunocytochemistry showed that NOBECs express the glial markers S100, GFAP (Glial Fibrillar Acid Protein) and p75NGFR as well as NRG1 (neuregulin-1) and ErbB1-2-3 receptors; while they are negative for ErbB4. Yet, NOBECs exhibit a high proliferation and migration basal activity and can be transducted with vectors carrying GFP (green fluorescent protein) and NRG1 cDNA. Functional stimulation by means of NRG1-III-beta3 overexpression through viral transduction induced a significant increase in cell proliferation rate while it had no effect on cell migration. Altogether, these results show that NOBEC cell line retain glial features both morphologically and functionally, responding to the NRG1/ErbB-mediated gliotrophic stimulus, and represents thus a good tool for in vitro assays of glial cell manipulation and for in vivo experimental studies of glial cell transplantation in the central and peripheral nervous system.