Résumé :
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Teashirt (Tshz) genes encode transcription factors conserved between flies and mammals. We show that mouse ureteric smooth muscle cell (SMC) precursors express Tshz3, and that Tshz3 null mutant mice have congenital hydronephrosis without anatomically-impaired urine flow. In vivo, failed ureteric muscle differentiation antedated urinary tract dilatation while ex vivo, wild-type but not mutant fetal proximal ureter segments contracted spontaneously. Moreover, the expression of myocardin, an essential component of the regulatory pathway for SMC differentiation, and of myocardin-dependent SMC genes was markedly downregulated in Tshz3-null mouse ureters prior to the onset of hydronephrosis. The data are consistent with a model in which Tshz3 expression is required for SMC differentiation by pathways involving myocardin-dependent SMC transcription. These findings provide new insights into molecular pathways linking visceral SMC differentiation with muscle function, and they also emphasise the central role of the proximal ureter in the physiological transit of fetal urine from the kidney to the urinary bladder, with defects leading to congenital hydronephrosis
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