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The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis

Mammalian Hedgehog (Hh) signaling plays key roles in embryogenesis and uniquely requires primary cilia. Functional analyses of several ciliogenesis-related genes led to the discovery of the developmental diseases known as ciliopathies. Hence, identification of mammalian factors that regulate cilioge...

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Autores principales: Yoshida, Saishu, Aoki, Katsuhiko, Fujiwara, Ken, Nakakura, Takashi, Kawamura, Akira, Yamada, Kohji, Ono, Masaya, Yogosawa, Satomi, Yoshida, Kiyotsugu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410489/
https://www.ncbi.nlm.nih.gov/pubmed/32758357
http://dx.doi.org/10.7554/eLife.57381
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author Yoshida, Saishu
Aoki, Katsuhiko
Fujiwara, Ken
Nakakura, Takashi
Kawamura, Akira
Yamada, Kohji
Ono, Masaya
Yogosawa, Satomi
Yoshida, Kiyotsugu
author_facet Yoshida, Saishu
Aoki, Katsuhiko
Fujiwara, Ken
Nakakura, Takashi
Kawamura, Akira
Yamada, Kohji
Ono, Masaya
Yogosawa, Satomi
Yoshida, Kiyotsugu
author_sort Yoshida, Saishu
collection PubMed
description Mammalian Hedgehog (Hh) signaling plays key roles in embryogenesis and uniquely requires primary cilia. Functional analyses of several ciliogenesis-related genes led to the discovery of the developmental diseases known as ciliopathies. Hence, identification of mammalian factors that regulate ciliogenesis can provide insight into the molecular mechanisms of embryogenesis and ciliopathy. Here, we demonstrate that DYRK2 acts as a novel mammalian ciliogenesis-related protein kinase. Loss of Dyrk2 in mice causes suppression of Hh signaling and results in skeletal abnormalities during in vivo embryogenesis. Deletion of Dyrk2 induces abnormal ciliary morphology and trafficking of Hh pathway components. Mechanistically, transcriptome analyses demonstrate down-regulation of Aurka and other disassembly genes following Dyrk2 deletion. Taken together, the present study demonstrates for the first time that DYRK2 controls ciliogenesis and is necessary for Hh signaling during mammalian development.
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spelling pubmed-74104892020-08-10 The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis Yoshida, Saishu Aoki, Katsuhiko Fujiwara, Ken Nakakura, Takashi Kawamura, Akira Yamada, Kohji Ono, Masaya Yogosawa, Satomi Yoshida, Kiyotsugu eLife Developmental Biology Mammalian Hedgehog (Hh) signaling plays key roles in embryogenesis and uniquely requires primary cilia. Functional analyses of several ciliogenesis-related genes led to the discovery of the developmental diseases known as ciliopathies. Hence, identification of mammalian factors that regulate ciliogenesis can provide insight into the molecular mechanisms of embryogenesis and ciliopathy. Here, we demonstrate that DYRK2 acts as a novel mammalian ciliogenesis-related protein kinase. Loss of Dyrk2 in mice causes suppression of Hh signaling and results in skeletal abnormalities during in vivo embryogenesis. Deletion of Dyrk2 induces abnormal ciliary morphology and trafficking of Hh pathway components. Mechanistically, transcriptome analyses demonstrate down-regulation of Aurka and other disassembly genes following Dyrk2 deletion. Taken together, the present study demonstrates for the first time that DYRK2 controls ciliogenesis and is necessary for Hh signaling during mammalian development. eLife Sciences Publications, Ltd 2020-08-06 /pmc/articles/PMC7410489/ /pubmed/32758357 http://dx.doi.org/10.7554/eLife.57381 Text en © 2020, Yoshida et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Yoshida, Saishu
Aoki, Katsuhiko
Fujiwara, Ken
Nakakura, Takashi
Kawamura, Akira
Yamada, Kohji
Ono, Masaya
Yogosawa, Satomi
Yoshida, Kiyotsugu
The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis
title The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis
title_full The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis
title_fullStr The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis
title_full_unstemmed The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis
title_short The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis
title_sort novel ciliogenesis regulator dyrk2 governs hedgehog signaling during mouse embryogenesis
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410489/
https://www.ncbi.nlm.nih.gov/pubmed/32758357
http://dx.doi.org/10.7554/eLife.57381
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