{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:26:06Z","timestamp":1789179966659,"version":"build-2803163510"},"reference-count":67,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004733","name":"Universidade de Macau","doi-asserted-by":"crossref","award":["MYRG2016-00072-FHS"],"award-info":[{"award-number":["MYRG2016-00072-FHS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004733","name":"Universidade de Macau","doi-asserted-by":"crossref","award":["CPG2020-00005-FHS"],"award-info":[{"award-number":["CPG2020-00005-FHS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004733","name":"Universidade de Macau","doi-asserted-by":"crossref","award":["MYRG2019-00123-FHS"],"award-info":[{"award-number":["MYRG2019-00123-FHS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004733","name":"Universidade de Macau","doi-asserted-by":"crossref","award":["MYRG2017-00157-FHS"],"award-info":[{"award-number":["MYRG2017-00157-FHS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Macau Fund for Development of Science and Technology","award":["FDCT173\/2017\/A3"],"award-info":[{"award-number":["FDCT173\/2017\/A3"]}]},{"name":"Macau Fund for Development of Science and Technology","award":["FDCT0132\/2019\/A3"],"award-info":[{"award-number":["FDCT0132\/2019\/A3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The Hippo signaling pathway is a kinase cascade that plays an important role in organ size control. As the main effectors of the Hippo pathway, transcription coactivators Yap1\/Wwtr1 are regulated by the upstream kinase Stk3. Recent studies in mammals have implicated the Hippo pathway in kidney development and kidney diseases. To further illustrate its roles in vertebrate kidney, we generated a series of zebrafish mutants targeting stk3, yap1 and wwtr1 genes. The stk3\u2212\/\u2212 mutant exhibited edema, formation of glomerular cysts and pronephric tubule dilation during the larval stage. Interestingly, disruption of wwtr1, but not yap1, significantly alleviated the renal phenotypes of the stk3\u2212\/\u2212 mutant, and overexpression of Wwtr1 with the CMV promoter also induced pronephric phenotypes, similar to those of the stk3\u2212\/\u2212 mutant, during larval stage. Notably, adult fish with Wwtr1 overexpression developed phenotypes similar to those of human polycystic kidney disease (PKD). Overall, our analyses revealed roles of Stk3 and Wwtr1 in renal cyst formation. Using a pharmacological approach, we further demonstrated that Stk3-deficient zebrafish could serve as a PKD model for drug development.<\/jats:p>","DOI":"10.1242\/dmm.049027","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T06:47:45Z","timestamp":1632206865000},"source":"Crossref","is-referenced-by-count":7,"title":["Novel zebrafish polycystic kidney disease models reveal functions of the Hippo pathway in renal cystogenesis"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9090-1632","authenticated-orcid":false,"given":"Zhiqin","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4296-1585","authenticated-orcid":false,"given":"Wei","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"2021110916410740100_DMM049027C1","doi-asserted-by":"publisher","first-page":"10189","DOI":"10.1038\/s41598-018-27657-x","article-title":"Zebrafish mutants and TEAD reporters reveal essential functions for Yap and Taz in posterior cardinal vein development","volume":"8","author":"Astone","year":"2018","journal-title":"Sci. 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