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Deletion of Atoh1 Disrupts Sonic Hedgehog Signaling in the Developing Cerebellum and Prevents Medulloblastoma

Science  04 Dec 2009:
Vol. 326, Issue 5958, pp. 1424-1427
DOI: 10.1126/science.1181453

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Abstract

Granule neuron precursors (GNPs) are the most actively proliferating cells in the postnatal nervous system, and mutations in pathways that control the GNP cell cycle can result in medulloblastoma. The transcription factor Atoh1 has been suspected to contribute to GNP proliferation, but its role in normal and neoplastic postnatal cerebellar development remains unexplored. We show that Atoh1 regulates the signal transduction pathway of Sonic Hedgehog, an extracellular factor that is essential for GNP proliferation, and demonstrate that deletion of Atoh1 prevents cerebellar neoplasia in a mouse model of medulloblastoma. Our data shed light on the function of Atoh1 in postnatal cerebellar development and identify a new mechanism that can be targeted to regulate medulloblastoma formation.

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