Expression of ATOH1 gene and activated signaling pathways for the neurogenesis of cerebellar granule cells: A review

Granule cells in the cerebellum are derived by the proliferation of cells from the rhombic lips of the metencephalon. Atonal homolog 1 (ATOH1), a protein encoding proneural gene, plays an essential role in the neurogenesis of the cerebellar granule cells. It encodes the basic helix loop helix (bHLH) family of transcription factor ATOH1. Expression of the ATOH1 gene in the rhombic lips of the metencephalon results in specification and proliferation of the granule neuron progenitors. Four major signaling pathways- Sonic hedgehog (Shh), Notch, Wingless related integration site (Wnt) and Bone morphogenetic protein (BMP) play an essential role in the regulation of the ATOH1 gene. Shh, Notch and Wnt signalings induce expression of the ATOH1 gene for the proliferation of the granule neuron progenitors whereas BMP signaling is involved in the differentiation of the granule neuron progenitors into the granule cells. Aberrant expression and mutation of the ATOH1 gene result in cerebellar medulloblastoma, the phenotype of trembling gait, cerebellar ataxia and hearing loss.