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GPR17 is an essential regulator for the temporal adaptation of Sonic hedgehog signalling in neural tube development

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dc.contributor.author Yatsuzuka, Atsuki en
dc.contributor.author Hori, Akiko en
dc.contributor.author Kadoya, Minori en
dc.contributor.author Matsuo-Takasaki, Mami en
dc.contributor.author Kondo, Toru en
dc.contributor.author Sasai, Noriaki en
dc.date.accessioned 2019-09-03T05:32:31Z en
dc.date.available 2019-09-03T05:32:31Z en
dc.date.issued 2019-08-23 en
dc.identifier.issn 0950-1991 en
dc.identifier.uri http://hdl.handle.net/10061/13373 en
dc.description.abstract Dorsal-ventral pattern formation of the neural tube is regulated by temporal and spatial activities of extracellular signalling molecules. Sonic hedgehog (Shh) assigns ventral neural subtypes via activation of the Gli transcription factors. Shh activity in the neural progenitor cells changes dynamically during differentiation, but the mechanisms regulating this dynamicity are not fully understood. Here we show that temporal change of the intracellular cAMP level confers the temporal Shh signal, and the purinergic-type G-protein coupled receptor GPR17 plays an essential role for this regulation. GPR17 is highly expressed in the ventral progenitor regions of the neural tube and acts as a negative regulator of the Shh signal in chick embryos. While the activation of the GPR17-related signal inhibits ventral identity, perturbation of GPR17 expression leads to aberrant expansion of ventral neural domains. Notably, perturbation of GPR17 expression partially inhibits the negative feedback of Gli activity. Moreover, GPR17 increases cAMP activity, suggesting that it exerts its function by inhibiting the processing of Gli3 protein. GPR17 also negatively regulates Shh signalling in neural cells differentiated from mouse embryonic stem cells, suggesting that GPR17 function is conserved among different organisms. Our results demonstrate that GPR17 is a novel negative regulator of Shh signalling in a wide range of cellular contexts. en
dc.language.iso en en
dc.publisher Company of Biologists: Development en
dc.rights © 2019. Published by The Company of Biologists Ltd ja
dc.rights 出版社許諾条件により、本文は2020年8月23日以降に公開 ja
dc.subject G-protein coupled recepto en
dc.subject Chick en
dc.subject Mouse embryonic stem cells en
dc.subject Neural tube en
dc.subject Sonic hedgehog, en
dc.subject Temporal adaptation en
dc.title GPR17 is an essential regulator for the temporal adaptation of Sonic hedgehog signalling in neural tube development en
dc.type.nii Journal Article en
dc.contributor.transcription ヤツズカ, アツキ ja
dc.contributor.transcription ホリ, アキコ ja
dc.contributor.transcription カドヤ, ミノリ ja
dc.contributor.transcription ササイ, ノリアキ ja
dc.contributor.alternative 八塚, 敦輝 ja
dc.contributor.alternative 堀, 晶子 ja
dc.contributor.alternative 角谷, 美典 ja
dc.contributor.alternative 笹井, 紀明 ja
dc.textversion author en
dc.identifier.abstracturl https://dev.biologists.org/content/early/2019/08/22/dev.176784.article-info en
dc.identifier.jtitle Development en
dc.relation.doi 10.1242/dev.176784 en
dc.identifier.NAIST-ID 84366327 en
dc.identifier.NAIST-ID 74652256 en
dc.identifier.NAIST-ID 85622108 en
dc.identifier.NAIST-ID 74651969 en
dc.relation.pmid 31444216 en

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