VIRAL TRANSDUCTION OF TRKA INTO CULTURED NODOSE AND SPINAL MOTOR-NEURONS CONVEYS NGF RESPONSIVENESS

The trkA gene encodes the tyrosine kinase receptor that transduces the NGF signal. We have used a defective herpes simplex virus-1 (HSV-1) v ector containing a full-length rat trkA sequence (pHSVtrkA) to express NGF receptors in primary cultures of neonatal nodose neurons and embr yonic spinal motor neurons which are normally unresponsive to NGF. Tra nsduction of rat neonatal nodose ganglion neurons and spinal motor neu rons with pHSVtrkA resulted in expression of functional NGF receptors. Stimulation of these receptors by NGF resulted in the survival and th e morphologic and biochemical differentiation of these neurons. These observations indicate that nodose and spinal motor neurons can express the downstream signal transduction apparatus necessary to mediate the survival and differentiating effects mediated by ligand binding to tr kA and that transduction with pHSVtrkA can effectively convert NGF non responsive neurons into responsive ones. (C) 1994 Academic Press, Inc.