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About 40%\u201050% of patients have kidney abnormalities, and frequently display multicystic, dysplastic kidneys. Additionally, gain\u2010of\u2010function mutations in\n                    <jats:italic>NOTCH2<\/jats:italic>\n                    are associated with cystic kidneys in Hajdu\u2010Cheney syndrome patients. How perturbations in Notch signaling cause renal tubular cysts remains unclear. Here, we have determined that reduced Notch signaling mediated transcription by ectopic expression of dominant\u2010negative mastermind\u2010like (dnMaml) peptide in the nephrogenic epithelia from after the s\u2010shaped body formation and in the developing collecting ducts results in proximal tubular and collecting duct cysts, respectively. An acute inhibition of Notch signaling for two days during kidney development is sufficient to disrupt tubule formation, and significantly increases\n                    <jats:italic>Akap12<\/jats:italic>\n                    expression. Ectopic expression of Akap12 in renal epithelia results in abnormally long primary cilia similar to that observed in Notch\u2010signaling\u2010deficient epithelia. Both loss of Notch signaling and elevated Akap12 expression disrupt the ability of renal epithelial cells to form spherical structures with a single lumen when grown embedded in matrix. Interestingly, Akap12 can inhibit Notch signaling mediated transcription, which likely explains how both loss of Notch signaling and ectopic expression of Akap12 result in similar renal epithelial abnormalities. We conclude that Notch signaling regulates\n                    <jats:italic>Akap12<\/jats:italic>\n                    expression while also ensuring normal primary cilia length and renal epithelial morphogenesis, and suggest that one aspect of diseases associated with defective Notch signaling, such as Alagille syndrome, maybe mechanistically related to ciliopathies.\n                  <\/jats:p>","DOI":"10.1096\/fj.201902358rr","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T10:37:08Z","timestamp":1595846228000},"page":"9512-9530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Notch signaling regulates\n                    <i>Akap12<\/i>\n                    expression and primary cilia length during renal tubule morphogenesis"],"prefix":"10.1096","volume":"34","author":[{"given":"Malini","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Pediatrics and Rare Diseases Group Sanford Research Sioux Falls SD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishara","family":"Ratnayake","sequence":"additional","affiliation":[{"name":"Department of Nanoscience and Nanoengineering South Dakota School of Mines and Technology Rapid City SD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhusudhana","family":"Janga","sequence":"additional","affiliation":[{"name":"Pediatrics and Rare Diseases Group Sanford Research Sioux Falls SD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Division of Basic Biomedical Sciences, Sanford School of Medicine University of South Dakota Vermillion SD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shania","family":"Scheidt","sequence":"additional","affiliation":[{"name":"Pediatrics and Rare Diseases Group Sanford Research Sioux Falls SD 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