DISTINCT ISOFORMS OF NEUREGULIN ARE EXPRESSED IN MESENCHYMAL AND NEURONAL CELLS DURING MOUSE DEVELOPMENT

Neuregulin, the putative ligand of the c-neu receptor tyrosine kinase, can induce differentiation or growth of epithelia and other cells. To gain insight into the biological role of this factor, we have analyze d the expression of neuregulin during mouse embryogenesis and in the p erinatal animal by a combination of in situ hybridization and RNase pr otection experiments. We identify sites of expression that correspond to mesenchymal cells of various parenchymal organs. Our finding implie s a function of neuregulin as a mesenchymal factor that acts on epithe lia. The mesenchymal expression of neuregulin could thus provide a mol ecular basis for the biological phenomenon of mesenchymal-epithelial i nteractions. It also has implications on the molecular mechanism by wh ich amplification of c-neu can affect tumor progression of carcinomas. In addition, neuregulin expression is found in neuronal cells during development. We show by RNase protection experiments that distinct iso forms of neuregulin are expressed in the brain. Therefore, our data in dicate in vivo a dual role for neuregulin as mesenchymal and neuronal factor.