Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret

Ekatherina Batourina, Christopher Choi, Neal Paragas, Natalie Bello, Terry Hensle, Frank D. Costantini, Anita Schuchardt, Robert L. Bacallao, Cathy L. Mendelsohn

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder. During development, ureters migrate by an unknown mechanism from their initial integration site in the Wolffian ducts up to the base of the bladder in a process that we call ureter maturation. Rara−/−Rarb2−/− mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret. Here we show that ureter maturation depends on formation of the 'trigonal wedge', a newly identified epithelial outgrowth from the base of the Wolffian ducts, and that the distal ureter abnormalities seen in Rara−/−Rarb2−/− and Ret−/− mutant mice are probably caused by a failure of this process. Our studies indicate that formation of the trigonal wedge may be essential for correct insertion of the distal ureters into the bladder, and that these events are mediated by the vitamin A and Ret signaling pathways.

Original languageEnglish (US)
Pages (from-to)109-115
Number of pages7
JournalNature Genetics
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2002

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Ureter
Vitamin A
Morphogenesis
Epithelial Cells
Wolffian Ducts
Urinary Bladder
Urogenital Abnormalities
Proto-Oncogenes
Hydronephrosis
Kidney
Mutation

Cite this

Batourina, E., Choi, C., Paragas, N., Bello, N., Hensle, T., Costantini, F. D., ... Mendelsohn, C. L. (2002). Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nature Genetics, 32(1), 109-115. https://doi.org/10.1038/ng952

Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. / Batourina, Ekatherina; Choi, Christopher; Paragas, Neal; Bello, Natalie; Hensle, Terry; Costantini, Frank D.; Schuchardt, Anita; Bacallao, Robert L.; Mendelsohn, Cathy L.

In: Nature Genetics, Vol. 32, No. 1, 01.01.2002, p. 109-115.

Research output: Contribution to journalArticle

Batourina, E, Choi, C, Paragas, N, Bello, N, Hensle, T, Costantini, FD, Schuchardt, A, Bacallao, RL & Mendelsohn, CL 2002, 'Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret', Nature Genetics, vol. 32, no. 1, pp. 109-115. https://doi.org/10.1038/ng952
Batourina E, Choi C, Paragas N, Bello N, Hensle T, Costantini FD et al. Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nature Genetics. 2002 Jan 1;32(1):109-115. https://doi.org/10.1038/ng952
Batourina, Ekatherina ; Choi, Christopher ; Paragas, Neal ; Bello, Natalie ; Hensle, Terry ; Costantini, Frank D. ; Schuchardt, Anita ; Bacallao, Robert L. ; Mendelsohn, Cathy L. / Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. In: Nature Genetics. 2002 ; Vol. 32, No. 1. pp. 109-115.
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