POTENTIATING INTERACTIONS BETWEEN MORPHOGENETIC PROTEIN AND NEUROTROPHIC FACTORS IN DEVELOPING NEURONS

mRNA for bone morphogenetic protein receptor type II (BMPR-II) was map ped to different neurons in peripheral ganglia and spinal cord of the chicken embryo. The expression of this serine/threonine kinase recepto r partially overlaps with that of tyrosine kinase receptors Trk and Re t, Biological activities of osteogenic protein-1 (OP-1), a documented ligand for BMPR-II, were tested in explanted embryonic chicken ganglia and dissociated ganglionic neurons. OP-1 had only a limited stimulato ry effect on neuronal survival. However, OP-1 combined with either neu rotrophin-3 (NT-3, a relative of nerve growth factor) or glial cell li ne-derived neurotrophic factor (GDNF) potentiated neuronal survival th ree- to fourfold. We also show that OP-1 strongly potentiates nerve fi ber outgrowth from ganglia stimulated with NT-3 or GDNF. Signaling by BMPR-II in neurons may potentiate the tyrosine kinase pathway activate d by NT-3 and GDNF, The data suggest that morphogenetic proteins may m odulate neurotrophic activities during neuronal development and plasti city. (C) 1998 Wiley-Liss, Inc.