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First published online 19 September 2007
doi: 10.1242/dev.011270

Development 134, 3763-3769 (2007)
Published by The Company of Biologists 2007
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The development of the bladder trigone, the center of the anti-reflux mechanism

Renata Viana1, Ekatherina Batourina1, Hongying Huang2, Gregory R. Dressler3, Akio Kobayashi4, Richard R. Behringer4, Ellen Shapiro2, Terry Hensle1, Sarah Lambert1 and Cathy Mendelsohn1,*

1 Columbia University, Department of Urology, 650 West 168th Street, New York, NY 10032, USA.
2 Department of Urology, New York University School of Medicine New York, NY, USA.
3 Department of Pathology, University of Michigan, MSRB1, BSRB 2049, 109 Zina Pitcher Dr, Ann Arbor, MI 481093, USA.
4 Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

* Author for correspondence (e-mail: hendelsohn{at}gmail.com)

Accepted 27 July 2007

The urinary tract is an outflow system that conducts urine from the kidneys to the bladder via the ureters that propel urine to the bladder via peristalsis. Once in the bladder, the ureteral valve, a mechanism that is not well understood, prevents backflow of urine to the kidney that can cause severe damage and induce end-stage renal disease. The upper and lower urinary tract compartments form independently, connecting at mid-gestation when the ureters move from their primary insertion site in the Wolffian ducts to the trigone, a muscular structure comprising the bladder floor just above the urethra. Precise connections between the ureters and the trigone are crucial for proper function of the ureteral valve mechanism; however, the developmental events underlying these connections and trigone formation are not well understood. According to established models, the trigone develops independently of the bladder, from the ureters, Wolffian ducts or a combination of both; however, these models have not been tested experimentally. Using the Cre-lox recombination system in lineage studies in mice, we find, unexpectedly, that the trigone is formed mostly from bladder smooth muscle with a more minor contribution from the ureter, and that trigone formation depends at least in part on intercalation of ureteral and bladder muscle. These studies suggest that urinary tract development occurs differently than previously thought, providing new insights into the mechanisms underlying normal and abnormal development.

Key words: Bladder, Reflux, Trigone, Ureter, Urinary tract formation, Mouse, Human






© The Company of Biologists Ltd 2007