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

Chia Hsiang Chang; Marco Zanini; Hamasseh Shirvani; Jia Shing Cheng; Hua Yu; Chih Hsin Feng; Audrey L. Mercier; Shiue Yu Hung; Antoine Forget; Chun Hung Wang; Sara Maria Cigna; I. Ling Lu; Wei Yi Chen; Sophie Leboucher; Won Jing Wang; Martial Ruat; Nathalie Spassky; Jin Wu Tsai; Olivier Ayrault

doi:10.1016/j.devcel.2018.12.017

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

Chia Hsiang Chang, Marco Zanini, Hamasseh Shirvani, Jia Shing Cheng, Hua Yu, Chih Hsin Feng, Audrey L. Mercier, Shiue Yu Hung, Antoine Forget, Chun Hung Wang, Sara Maria Cigna, I. Ling Lu, Wei Yi Chen, Sophie Leboucher, Won Jing Wang, Martial Ruat, Nathalie Spassky, Jin Wu Tsai^*, Olivier Ayrault

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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.

原文	English
頁（從 - 到）	184-199.e5
期刊	Developmental Cell
卷	48
發行號	2
DOIs	https://doi.org/10.1016/j.devcel.2018.12.017
出版狀態	Published - 28 1月 2019

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Chang, C. H., Zanini, M., Shirvani, H., Cheng, J. S., Yu, H., Feng, C. H., Mercier, A. L., Hung, S. Y., Forget, A., Wang, C. H., Cigna, S. M., Lu, I. L., Chen, W. Y., Leboucher, S., Wang, W. J., Ruat, M., Spassky, N., Tsai, J. W., & Ayrault, O. (2019). Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation. Developmental Cell, 48(2), 184-199.e5. https://doi.org/10.1016/j.devcel.2018.12.017

@article{511b85339eb14d2bb1015185dcb3a19f,

title = "Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation",

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.",

keywords = "Atoh1 (Math1), Cep131 (Azi1), Pcm1, centriolar satellites, cerebellar development, granule neuron progenitors, medulloblastoma, primary cilium, sonic hedgehog",

author = "Chang, {Chia Hsiang} and Marco Zanini and Hamasseh Shirvani and Cheng, {Jia Shing} and Hua Yu and Feng, {Chih Hsin} and Mercier, {Audrey L.} and Hung, {Shiue Yu} and Antoine Forget and Wang, {Chun Hung} and Cigna, {Sara Maria} and Lu, {I. Ling} and Chen, {Wei Yi} and Sophie Leboucher and Wang, {Won Jing} and Martial Ruat and Nathalie Spassky and Tsai, {Jin Wu} and Olivier Ayrault",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2019",

month = jan,

day = "28",

doi = "10.1016/j.devcel.2018.12.017",

language = "English",

volume = "48",

pages = "184--199.e5",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "2",

}

Chang, CH, Zanini, M, Shirvani, H, Cheng, JS, Yu, H, Feng, CH, Mercier, AL, Hung, SY, Forget, A, Wang, CH, Cigna, SM, Lu, IL, Chen, WY, Leboucher, S, Wang, WJ, Ruat, M, Spassky, N, Tsai, JW & Ayrault, O 2019, 'Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation', Developmental Cell, 卷 48, 編號 2, 頁 184-199.e5. https://doi.org/10.1016/j.devcel.2018.12.017

TY - JOUR

T1 - Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation

AU - Chang, Chia Hsiang

AU - Zanini, Marco

AU - Shirvani, Hamasseh

AU - Cheng, Jia Shing

AU - Yu, Hua

AU - Feng, Chih Hsin

AU - Mercier, Audrey L.

AU - Hung, Shiue Yu

AU - Forget, Antoine

AU - Wang, Chun Hung

AU - Cigna, Sara Maria

AU - Lu, I. Ling

AU - Chen, Wei Yi

AU - Leboucher, Sophie

AU - Wang, Won Jing

AU - Ruat, Martial

AU - Spassky, Nathalie

AU - Tsai, Jin Wu

AU - Ayrault, Olivier

PY - 2019/1/28

Y1 - 2019/1/28

N2 - 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.

AB - 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.

KW - Atoh1 (Math1)

KW - Cep131 (Azi1)

KW - Pcm1

KW - centriolar satellites

KW - cerebellar development

KW - granule neuron progenitors

KW - medulloblastoma

KW - primary cilium

KW - sonic hedgehog

UR - http://www.scopus.com/inward/record.url?scp=85059778584&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2018.12.017

DO - 10.1016/j.devcel.2018.12.017

M3 - Article

C2 - 30695697

AN - SCOPUS:85059778584

SN - 1534-5807

VL - 48

SP - 184-199.e5

JO - Developmental Cell

JF - Developmental Cell

IS - 2

ER -

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

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