Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype...

Bone morphogenetic proteins are members of the transforming growth factor-beta superfamily. They are widely expressed in the mammalian nervous system, where they exert trophic effects on several neuronal populations. We studied the neurotrophic activity of bone morphogenetic protein-2 and bone morphogenetic protein-7 (also called osteogenic protein-1) on cultured striatal cells, previously shown to express bone morphogenetic protein ligands and receptors. Our results indicate that only bone morphogenetic protein-2 promoted the differentiation of GABAergic neurons, especially of the calbindin-positive subpopulation, the subset of projecting striatal neurons that degenerates in Huntington's disease. Bone morphogenetic protein-2 increased the area, perimeter and degree of arborization of GABAergic neurons, promoting calbindin phenotype without altering proliferation or apoptosis. In contrast, neither bone morphogenetic protein-2 nor -7 affected striatal cholinergic interneurons. However, they both increased the number of glial fibrillary acidic protein-positive cells. Suppression of glial proliferation with 5-fluorodeoxyuridine did not abolish bone morphogenetic protein-2 effects on the differentiation of striatal neurons, ruling out an indirect mechanism through astrocytes. In conclusion, our results show that bone morphogenetic protein-2 promotes the differentiation of cultured GABAergic striatal neurons, suggesting that bone morphogenetic proteins are involved in the development of the striatum.