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

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.