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Abstract
Mutations in GLI3, a component of the Sonic Hedgehog (Shh) signaling pathway, cause a variety of human developmental syndromes. In this issue of the JCI, Cain and colleagues show that tightly regulated GLI3 repressor activity is essential for Shh-dependent differentiation of upper urinary tract pacemaker cells and the efficient flow of urine from the kidney to the bladder. These results link defective pacemaker cell differentiation with hydronephrosis and provide a cellular basis for one of the abnormal renal defects observed in humans with the GLI3-linked disease Pallister-Hall syndrome.
Authors
Doris Herzlinger
Figure 1
The kidney outflow tract includes the renal calyces, pelvis, and ureter and is highly prone to congenital defects.
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Abnormalities that severely impair the flow of urine through the outflow tract lead to hydronephrosis and often permanent kidney damage. Known causes of hydronephrosis include outflow tract compression by ectopic renal vessels, structural occlusions intrinsic to the outflow tract, and aberrant outflow tract smooth muscle differentiation that results in aperistaltic ureter segments. The report by Cain et al. (13 ) shows that hydronephrosis can also be caused by inefficient, dysplastic peristalsis caused by an absence of upper urinary tract pacemakers, the specialized cells that trigger smooth muscle contractions.
Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)