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Data from: Hedgehog pathway disruption alters urothelial differentiation and continence mechanisms in the female mouse lower urinary tract

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Feb 19, 2026 version files 9.25 GB

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Abstract

Urinary incontinence (UI) imposes a significant healthcare burden and reduces quality of life. Contributing factors such as aging, pregnancy/childbirth, stress, and injury are recognized, but an incomplete understanding of underlying mechanisms limits new therapies. Hedgehog (Hh) signaling has been implicated in lower urinary tract development, but its specific role in female continence mechanisms has not been fully characterized. Here, we investigate the functional and molecular consequences of reduced Hh signaling using Gli2+/-;Gli3Δ699/+, (Gli mutant) female mice. We assessed spontaneous voiding through void spot assays and uroflowmetry, then assessed contractility in bladder and urethral tissues ex vivo. Female Gli mutant mice display more small-volume voids than wild-type mice. Gli mutant female bladders had reduced contractile strength to electrical field and cholinergic stimuli, while the urethra had reduced sensitivity to serotonin-mediated contraction, but not to phenylephrine. Thus, unique changes to bladder and urethral contractility dynamics are present in Gli mutant mice and are dependent upon the type of stimuli. Further, expression of serotonin transporter (Sert) mRNA was increased in the Gli mutant urethra compared to the wild type. Uroplakin IIIa, typically localized to bladder urothelium, was ectopically expressed in urethral urothelium of adult but not embryonic (E) day 16 Gli mutant mice. These findings highlight a previously uncharacterized role of Hh signaling in maintaining female lower urinary tract function and urothelial patterning, and support further investigation of its contribution to continence.