The development of the bladder trigone, the center of the anti-reflux mechanism

Abstract

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.

Pkd1-inactivation in vascular smooth muscle cells and adaptation to hypertension

“…Expression of the promoter in specific mesenchymal cells during the development may explain the observed expression pattern. 37 Despite the presence of large cysts, the function of the pancreas was not severely affected, as no loss of acini was found and there was no starch present in the colon, indicating a sufficient level of digestion (not shown). In the liver, no loss of hepatocytes was noticed either.…”

The physiological function of lower urinary tract smooth muscle

“…Anatomically it is demarcated as the triangular region between the ureteral openings and the bladder outlet. The region was believed to have a mesodermal origin, but more recent studies suggest rather that the trigone is formed predominantly from bladder muscle; and the contribution from ureteral longitudinal fibers is more limited (Viana et al, 2007).…”

TNXB Mutations Can Cause Vesicoureteral Reflux

“…4,5 Recent murine distal ureter genetic and developmental modeling studies implicated a significant contribution of disordered bladder trigone and common nephric duct interactions in PVUR development. [6][7][8][9][10][11][12][13] Although these theories provide explanations for early events during embryogenesis that are likely to give rise to renal dysplasia and VUR, they do not completely explain the pathogenesis of PVUR. VUR is highly heritable, and although many loci have been found, the specific genes encoded by these loci have remained elusive.…”