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.