BMPs oppose Math1 in cerebellar development and in medulloblastoma.

Bone morphogenetic proteins (BMPs) are soluble effectors of differentiation and are central in orchestrating development of organs including the cerebellum. The transcription factor and BMP target Math1 (mouse atonal homolog 1) is a critical regulator of neuronal progenitors destined to form the cerebellar cortex. Signaling networks controlled by BMPs, Math1, and Sonic Hedgehog (Shh) together regulate the proliferation and differentiation of cerebellar progenitor cells. Defects in these pathways are also implicated in medulloblastoma, the most common pediatric brain tumor. In this issue of Genes & Development, Zhao et al. (2008) perform an elegant set of experiments that clarify the role of BMPs and of Math1 in medulloblastoma. Destabilization of Math1 by treatment with BMP-2 or BMP-4 induced neuronal differentiation in cells from mouse models of Shh-driven medulloblastoma and reduced proliferation in established tumors in vivo. These studies provide important new insights into the vulnerabilities of medulloblastoma and present future therapeutic promise.