Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation

被引：58

作者：

Chang, Chia-Hsiang ^{[1
,2
,3
]}

Zanini, Marco ^{[4
,5
]}

Shirvani, Hamasseh ^{[4
,5
]}

Cheng, Jia-Shing ^{[1
]}

Yu, Hua ^{[4
,5
]}

Feng, Chih-Hsin ^{[1
]}

Mercier, Audrey L. ^{[4
,5
]}

Hung, Shiue-Yu ^{[6
]}

Forget, Antoine ^{[4
,5
]}

Wang, Chun-Hung ^{[1
]}

Cigna, Sara Maria ^{[4
,5
]}

Lu, I-Ling ^{[1
]}

Chen, Wei-Yi ^{[7
]}

Leboucher, Sophie ^{[4
,5
]}

Wang, Won-Jing ^{[7
]}

Ruat, Martial ^{[8
]}

Spassky, Nathalie ^{[9
,10
,11
]}

Tsai, Jin-Wu ^{[1
,12
,13
]}

Ayrault, Olivier ^{[4
,5
]}

机构：

[1] Natl Yang Ming Univ, Inst Brain Sci, Sch Med, Taipei 112, Taiwan

[2] Natl Yang Ming Univ, Taiwan Int Grad Program Mol Med, Taipei 112, Taiwan

[3] Acad Sinica, Taipei 112, Taiwan

[4] PSL Res Univ, Inst Curie, CNRS UMR 3347, INSERM U1021, F-91405 Orsay, France

[5] Univ Paris Sud, Univ Paris Saclay, CNRS UMR 3347, INSERM U1021, F-91405 Orsay, France

[6] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei 112, Taiwan

[7] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Coll Life Sci, Taipei 112, Taiwan

[8] Neurosci Paris Saclay Inst, CNRS, UMR 9197, F-91198 Paris, France

[9] ENS, Inst Biol, IBENS, F-75005 Paris, France

[10] CNRS, UMR8197, F-75005 Paris, France

[11] INSERM, U1024, F-75005 Paris, France

[12] Natl Yang Ming Univ, Brain Res Ctr, Taipei 112, Taiwan

[13] Natl Yang Ming Univ, Biophoton & Mol Imaging Res Ctr, Taipei 112, Taiwan

来源：

DEVELOPMENTAL CELL | 2019年 / 48卷 / 02期

关键词：

CENTRIOLAR SATELLITE INTEGRITY; SONIC HEDGEHOG; TRANSCRIPTIONAL ACTIVATION; TUMOR SUPPRESSORS; MEDULLOBLASTOMA; CEREBELLUM; DIFFERENTIATION; MATH1; GENE; EXPANSION;

D O I：

10.1016/j.devcel.2018.12.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：184 / +

页数：21

共 74 条

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