Potentiating interactions between morphogenetic protein and neurotrophic factors in developing neurons

mRNA for bone morphogenetic protein receptor type II (BMPR‐II) was mapped to different neurons in peripheral ganglia and spinal cord of the chicken embryo. The expression of this serine/threonine kinase receptor partially overlaps with that of tyrosine kinase receptors Trk and Ret. 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 stimulatory effect on neuronal survival. However, OP‐1 combined with either neurotrophin‐3 (NT‐3, a relative of nerve growth factor) or glial cell line–derived neurotrophic factor (GDNF) potentiated neuronal survival three‐ to fourfold. We also show that OP‐1 strongly potentiates nerve fiber outgrowth from ganglia stimulated with NT‐3 or GDNF. Signaling by BMPR‐II in neurons may potentiate the tyrosine kinase pathway activated by NT‐3 and GDNF. The data suggest that morphogenetic proteins may modulate neurotrophic activities during neuronal development and plasticity. J. Neurosci. Res. 53:559–568, 1998. © 1998 Wiley‐Liss, Inc.