Chromatin occupancy by Tox3 in mouse cerebellum
The cerebellum is a key component of the central nervous system in vertebrates. During vertebrate evolution and mammalian postnatal development, the cerebellum has expanded dramatically in size and complexity. The development and expansion of cerebellum requires the coordination of multiple biological events, which are not well understood. In this study, an unbiased organ-wise comparative transcriptomic analysis identifies the transcription factor Tox3, a member the high mobility group box family, as an essential regulator of cerebellum development and expansion. Inactivation of Tox3 in mice leads to ataxia and cerebellar hypoplasia. Furthermore, there is severely impairment in the proliferation of granule neuron progenitor cells, which undergo premature differentiation into granule cells. Mechanistically, Tox3 targets Atoh1 downstream enhancer to regulate its transcription and primary cilium formation. These findings reveal Tox3 as a missing link in the process of cerebellum expansion.