{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:27:41Z","timestamp":1790818061314,"version":"4.1.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[1999,3,15]],"date-time":"1999-03-15T00:00:00Z","timestamp":921456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The essential role of vitamin A and its metabolites, retinoids, in kidney development has been demonstrated in vitamin A deficiency and gene targeting studies. Retinoids signal via nuclear transcription factors belonging to the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families. Inactivation of RAR\u03b1 and RAR\u03b22 receptors together, but not singly, resulted in renal malformations, suggesting that within a given renal cell type, their concerted function is required for renal morphogenesis. At birth, RAR\u03b1\u03b22\u2212mutants displayed small kidneys, containing few ureteric bud branches, reduced numbers of nephrons and lacking the nephrogenic zone where new nephrons are continuously added. These observations have prompted us to investigate the role of RAR\u03b1 and RAR\u03b22 in renal development in detail. We have found that within the embryonic kidney, RAR\u03b1 and RAR\u03b22 are colocalized in stromal cells, but not in other renal cell types, suggesting that stromal cells mediate retinoid-dependent functions essential for renal development. Analysis of RAR\u03b1\u03b22\u2212 mutant kidneys at embryonic stages revealed that nephrons were formed and revealed no changes in the intensity or distribution of molecular markers specific for different metanephric mesenchymal cell types. In contrast the development of the collecting duct system was greatly impaired in RAR\u03b1\u03b22\u2212 mutant kidneys. Fewer ureteric bud branches were present, and ureteric bud ends were positioned abnormally, at a distance from the renal capsule. Analysis of genes important for ureteric bud morphogenesis revealed that the proto-oncogene c-ret was downregulated. Our results suggest that RAR\u03b1 and RAR\u03b22 are required for generating stromal cell signals that maintain c-ret expression in the embryonic kidney. Since c-ret signaling is required for ureteric bud morphogenesis, loss of c-ret expression is a likely cause of impaired ureteric bud branching in RAR\u03b1\u03b22\u2212 mutants.<\/jats:p>","DOI":"10.1242\/dev.126.6.1139","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:57:51Z","timestamp":1619409471000},"page":"1139-1148","source":"Crossref","is-referenced-by-count":235,"title":["Stromal cells mediate retinoid-dependent functions essential for renal development"],"prefix":"10.1242","volume":"126","author":[{"given":"Cathy","family":"Mendelsohn","sequence":"first","affiliation":[{"name":"Columbia University 1 , Department of Urology, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekatherina","family":"Batourina","sequence":"additional","affiliation":[{"name":"Columbia University 1 , Department of Urology, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suquin","family":"Fung","sequence":"additional","affiliation":[{"name":"Columbia University 2 , Department of Physiology and Biophysics, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Gilbert","sequence":"additional","affiliation":[{"name":"3 INSERM U319 \u2018Normal and pathological development of epithelial functions\u2019, University Paris 7, 75251 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Dodd","sequence":"additional","affiliation":[{"name":"Columbia University 2 , Department of Physiology and Biophysics, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,3,15]]},"reference":[{"key":"2023090516055271600_DEVELOP_126_6_1139C1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1083\/jcb.105.1.599","article-title":"Epithelial-mesenchymal interactions in the developing kidney lead to expression of tenascin in the mesenchyme","volume":"105","author":"Aufderheide","year":"1987","journal-title":"J. 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