Notch signaling is a novel regulator of visceral smooth muscle cell differentiation in the murine ureter.

The contractile phenotype of smooth muscle cells (SMCs) is transcriptionally controlled by a complex of the DNA-binding protein SRF and the transcriptional co-activator MYOCD. The pathways that activate expression of Myocd and of SMC structural genes in mesenchymal progenitors are diverse, reflecting different intrinsic and extrinsic signaling inputs. Taking the ureter as a model, we analyzed whether Notch signaling, a pathway previously implicated in vascular SMC development, also affects visceral SMC differentiation. We show that mice with a conditional deletion of the unique Notch mediator RBPJ in the undifferentiated ureteric mesenchyme exhibit altered ureter peristalsis with a delayed onset, and decreased contraction frequency and intensity at fetal stages. They also develop hydroureter 2 weeks after birth. Notch signaling is required for precise temporal activation of Myocd expression and, independently, for expression of a group of late SMC structural genes. Based on additional expression analyses, we suggest that a mesenchymal JAG1-NOTCH2/NOTCH3 module regulates visceral SMC differentiation in the ureter in a biphasic and bimodal manner, and that its molecular function differs from that in the vascular system. © 2022. Published by The Company of Biologists Ltd.

Citation

Jennifer Kurz, Anna-Carina Weiss, Hauke Thiesler, Fairouz Qasrawi, Lena Deuper, Jaskiran Kaur, Carsten Rudat, Timo H Lüdtke, Irina Wojahn, Herbert Hildebrandt, Mark-Oliver Trowe, Andreas Kispert. Notch signaling is a novel regulator of visceral smooth muscle cell differentiation in the murine ureter. Development (Cambridge, England). 2022 Feb 15;149(4)

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PMID: 35103284

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