Generation of cerebellar granule neurons in vivo by transplantation of BMP-treated neural progenitor cells

Cerebellar granule neurons, the most abundant class of CNS neurons, have a critical role in cerebellar function. Granule neurons are generated at the dorsal border of the mesencephalon and metencephalon, the rhombic lip. In t he mouse embryo, rhombic lip cells express a number of granule neuron marke rs, notably the bHLH transcription factor Math1. Dorsal midline cells adjac ent to the rhombic lip express Bmp6, Bmp7 and Gdf7, three genes encoding pe ptide growth factors of the bone morphogenetic protein (BMP) family. These BMPs induced the expression of granule neuron markers in cultured neural ti ssue. Moreover, BMP-treated neural cells formed mature granule neurons afte r transplantation into the early postnatal cerebellum, suggesting that BMPs initiate the program of granule cell specification.