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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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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. |
format | Online Article Text |
id | pubmed-7410489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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