{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:35:58Z","timestamp":1791286558853,"version":"4.1.0"},"reference-count":31,"publisher":"The Company of Biologists","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:p>Despite the high occurrence of congenital abnormalities of the lower urinary tract in humans, the molecular, cellular and morphological aspects of their development are still poorly understood. Here, we use a conditional knockout approach to inactivate within the nephric duct (ND) lineage the two effectors of the Hippo pathway, Yap and Taz. Deletion of Yap leads to hydronephrotic kidneys with blind-ending megaureters at birth. In Yap mutants, the ND successfully migrates towards, and contacts, the cloaca. However, close analysis reveals that the tip of the Yap\u2212\/\u2212 ND forms an aberrant connection with the cloaca and does not properly insert into the cloaca, leading to later detachment of the ND from the cloaca. Taz deletion from the ND does not cause any defect, but analysis of Yap\u2212\/\u2212;Taz\u2212\/\u2212 NDs indicates that both genes play partially redundant roles in ureterovesical junction formation. Aspects of the Yap\u2212\/\u2212 phenotype resemble hypersensitivity to RET signaling, including excess budding of the ND, increased phospho-ERK and increased expression of Crlf1, Sprouty1, Etv4 and Etv5. Importantly, the YapND\u2212\/\u2212 ND phenotype can be largely rescued by reducing Ret gene dosage. Taken together, these results suggest that disrupting Yap\/Taz activities enhances Ret pathway activity and contributes to pathogenesis of lower urinary tract defects in human infants.<\/jats:p>","DOI":"10.1242\/dev.122044","type":"journal-article","created":{"date-parts":[[2015,8,4]],"date-time":"2015-08-04T11:19:01Z","timestamp":1438687141000},"page":"2696-2703","source":"Crossref","is-referenced-by-count":53,"title":["Yap and Taz are required for Ret-dependent urinary tract morphogenesis"],"prefix":"10.1242","volume":"142","author":[{"given":"Antoine","family":"Reginensi","sequence":"first","affiliation":[{"name":"Lunenfeld\u2013Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada\u2008M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (Renal Division) and Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami Kamel","family":"Boualia","sequence":"additional","affiliation":[{"name":"Goodman Cancer Research Centre and\u2008Department of Biochemistry, McGill University, Montreal, Canada\u2008H3A 1A3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Goodman Cancer Research Centre and\u2008Department of Biochemistry, McGill University, Montreal, Canada\u2008H3A 1A3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Jain","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (Renal Division) and Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McNeill","sequence":"additional","affiliation":[{"name":"Lunenfeld\u2013Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada\u2008M5G 1X5"},{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Canada\u2008M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608082251600_DEV122044C1","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1172\/JCI26027","article-title":"Tbx18 regulates the development of the ureteral mesenchyme","volume":"116","author":"Airik","year":"2006","journal-title":"J. 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