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

Abstract

Medulloblastoma and Atoh1 The Atoh1 transcription factor is needed for normal brain development and is also implicated in some cancers of the brain. In order to study the latter function and avoid the perinatal lethality that follows early disruption of the Atoh1 gene, Flora et al. (p. 1424 ) knocked out the Atoh1 gene in mice after birth. A few days after the genetic knockout, cells at the surface of the cerebellum had begun to differentiate earlier than normal. Overexpression of Atoh1 , on the other hand, led to excessive cell growth and even preneoplastic lesions at the surface of the cerebellum. Atoh1 was found to regulate expression of the Gli2 gene, and thereby Sonic Hedgehog signaling, which normally keeps cerebellar precursor cells undifferentiated.