Bone morphogenetic protein-7 enhances dendritic growth and receptivity to innervation in cultured hippocampal neurons

Members of the bone morphogenetic protein (BMP) family of growth factors ar e present in the central nervous system during development and throughout l ife. They are known to play an important regulatory role in cell differenti ation, but their function in postmitotic telencephalic neurons has not been investigated. To address this question, we examined cultured hippocampal n eurons following treatment with bone morphogenetic protein-7 (BMP-7, also r eferred to as osteogenic protein-1). When added at the time of plating, BMP -7 markedly stimulated the rate of dendritic development. Within 1 day, the dendritic length of BMP-7-treated neurons was more than twice that of cont rols. By three days the dendritic arbors of BMP-7-treated neurons had attai ned a level of branching similar to that of e-week-old neurons cultured und er standard conditions. Several findings indicate that BMP-7 selectively en hances dendritic development. While dendritic length was significantly incr eased in BMP-7-treated neurons, the length of the axon was not. In addition , the mRNA encoding the dendritic protein MAP2 was significantly increased by BMP-7 treatment, but the mRNA for tubulin was not. Finally, BMP-7 did no t enhance cell survival. Because dendritic maturation is a rate-limiting st ep in synapse formation in hippocampal cultures, we examined whether BMP-7 accelerated the rate at which neurons became receptive to innervation. Usin g two separate experimental paradigms, we found that the rate of synapse fo rmation (assessed by counting synapsin l-positive presynaptic vesicle clust ers) was increased significantly in neurons that had been exposed previousl y to BMP-7. Because BMP-7 and related BMPs are expressed in the hippocampus in situ, these factors may play a role in regulating dendritic branching a nd synapse formation in both development and plasticity.