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Article: Loss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9

TitleLoss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9
Authors
KeywordsChondrodysplasia
YAP1
Chondrocytes
Mouse
TAZ
MOB1
WWTR1
SOX9
Issue Date2018
Citation
Development, 2018, v. 145, n. 6, article no. dev159244 How to Cite?
AbstractHippo signaling is modulated in response to cell density, external mechanical forces, and rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown. Cartilage is rich in ECM and also subject to strong external forces – two upstream factors regulating Hippo signaling. Chondrogenesis and endochondral ossification are tightly controlled by growth factors, morphogens, hormones, and transcriptional factors that engage in crosstalk with Hippo-YAP1/TAZ signaling. Here, we generated tamoxifen-inducible, chondrocyte-specific Mob1a/b-deficient mice and show that hyperactivation of endogenous YAP1/TAZ impairs chondrocyte proliferation and differentiation/maturation, leading to chondrodysplasia. These defects were linked to suppression of SOX9, a master regulator of chondrogenesis, the expression of which is mediated by TEAD transcription factors. Our data indicate that a MOB1- dependent YAP1/TAZ-TEAD complex functions as a transcriptional repressor of SOX9 and thereby negatively regulates chondrogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/293077
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.852
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGoto, Hiroki-
dc.contributor.authorNishio, Miki-
dc.contributor.authorTo, Yoko-
dc.contributor.authorOishi, Tatsuya-
dc.contributor.authorMiyachi, Yosuke-
dc.contributor.authorMaehama, Tomohiko-
dc.contributor.authorNishina, Hiroshi-
dc.contributor.authorAkiyama, Haruhiko-
dc.contributor.authorMak, Tak Wah-
dc.contributor.authorMakii, Yuma-
dc.contributor.authorSaito, Taku-
dc.contributor.authorYasoda, Akihiro-
dc.contributor.authorTsumaki, Noriyuki-
dc.contributor.authorSuzuki, Akira-
dc.date.accessioned2020-11-17T14:57:49Z-
dc.date.available2020-11-17T14:57:49Z-
dc.date.issued2018-
dc.identifier.citationDevelopment, 2018, v. 145, n. 6, article no. dev159244-
dc.identifier.issn0950-1991-
dc.identifier.urihttp://hdl.handle.net/10722/293077-
dc.description.abstractHippo signaling is modulated in response to cell density, external mechanical forces, and rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown. Cartilage is rich in ECM and also subject to strong external forces – two upstream factors regulating Hippo signaling. Chondrogenesis and endochondral ossification are tightly controlled by growth factors, morphogens, hormones, and transcriptional factors that engage in crosstalk with Hippo-YAP1/TAZ signaling. Here, we generated tamoxifen-inducible, chondrocyte-specific Mob1a/b-deficient mice and show that hyperactivation of endogenous YAP1/TAZ impairs chondrocyte proliferation and differentiation/maturation, leading to chondrodysplasia. These defects were linked to suppression of SOX9, a master regulator of chondrogenesis, the expression of which is mediated by TEAD transcription factors. Our data indicate that a MOB1- dependent YAP1/TAZ-TEAD complex functions as a transcriptional repressor of SOX9 and thereby negatively regulates chondrogenesis.-
dc.languageeng-
dc.relation.ispartofDevelopment-
dc.subjectChondrodysplasia-
dc.subjectYAP1-
dc.subjectChondrocytes-
dc.subjectMouse-
dc.subjectTAZ-
dc.subjectMOB1-
dc.subjectWWTR1-
dc.subjectSOX9-
dc.titleLoss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1242/dev.159244-
dc.identifier.pmid29511023-
dc.identifier.scopuseid_2-s2.0-85044292190-
dc.identifier.volume145-
dc.identifier.issue6-
dc.identifier.spagearticle no. dev159244-
dc.identifier.epagearticle no. dev159244-
dc.identifier.eissn1477-9129-
dc.identifier.isiWOS:000427697300010-
dc.identifier.issnl0950-1991-

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