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Science 326 (5958): 1424-1427

Copyright © 2009 by the American Association for the Advancement of Science

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

Adriano Flora,1 Tiemo J. Klisch,1,2 Gabriele Schuster,1 Huda Y. Zoghbi1,2,3,4,*

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.

1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
2 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
3 Departments of Neuroscience and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
4 Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.

* To whom correspondence should be addressed. E-mail: hzoghbi{at}

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