| Literature DB >> 30695697 |
Chia-Hsiang Chang1, Marco Zanini2, Hamasseh Shirvani2, Jia-Shing Cheng3, Hua Yu2, Chih-Hsin Feng3, Audrey L Mercier2, Shiue-Yu Hung4, Antoine Forget2, Chun-Hung Wang3, Sara Maria Cigna2, I-Ling Lu3, Wei-Yi Chen5, Sophie Leboucher2, Won-Jing Wang5, Martial Ruat6, Nathalie Spassky7, Jin-Wu Tsai8, Olivier Ayrault9.
Abstract
During cerebellar development, granule neuron progenitors (GNPs) proliferate by transducing Sonic Hedgehog (SHH) signaling via the primary cilium. Precise regulation of ciliogenesis, thus, ensures proper GNP pool expansion. Here, we report that Atoh1, a transcription factor required for GNPs formation, controls the presence of primary cilia, maintaining GNPs responsiveness to SHH. Loss of primary cilia abolishes the ability of Atoh1 to keep GNPs in a proliferative state. Mechanistically, Atoh1 promotes ciliogenesis by transcriptionally regulating Cep131, which facilitates centriolar satellite (CS) clustering to the basal body. Importantly, ectopic expression of Cep131 counteracts the effects of Atoh1 loss in GNPs by restoring proper localization of CS and ciliogenesis. This Atoh1-CS-primary cilium-SHH pro-proliferative pathway is also conserved in SHH-type medulloblastoma, a pediatric brain tumor arising from the GNPs. Together, our data reveal how Atoh1 modulates the primary cilium to regulate GNPs development.Entities:
Keywords: Atoh1 (Math1); Cep131 (Azi1); Pcm1; centriolar satellites; cerebellar development; granule neuron progenitors; medulloblastoma; primary cilium; sonic hedgehog
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Year: 2019 PMID： 30695697 DOI： 10.1016/j.devcel.2018.12.017
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270