Transcription factor Tcf21 modulates urinary bladder size and differentiation

Urinary bladder organogenesis requires coordinated cell growth, specification, and patterning of both mesenchymal and epithelial compartments. Tcf21, a gene that encodes a helix-loop-helix transcription factor, is specifically expressed in the mesenchyme of the bladder during development. Here we show that Tcf21 is required for normal development of the bladder. We found that the bladders of mice lacking Tcf21 were notably hypoplastic and that the Tcf21 mutant mesenchyme showed increased apoptosis. There was also a marked delay in the formation of visceral smooth muscle, accompanied by a defect in myocardin (Myocd) expression. Interestingly, there was also a marked delay in the formation of the basal cell layer of the urothelium, distinguished by diminished expression of Krt5 and Krt14. Our findings suggest that Tcf21 regulates the survival and differentiation of mesenchyme cell-autonomously and the maturation of the adjacent urothelium non-cell-autonomously during bladder development. Genetic deletion of the mesenychymal transcription factor Tcf21 in mice results in a hypoplastic bladder. We show that Tcf21 regulates mesenchymal cell survival as well as the temporal differentiation of smooth muscle. In addition, we found that deletion of Tcf21 exhibits a non-cell-autonomous effect on the maturation of the urothelium.image