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, and develop hydroureter two 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-NOTCH2/3 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.
Notch signaling is a novel regulator of visceral smooth muscle cell differentiation in the murine ureter
These authors contributed equally to this work
- Award Group:
- Funder(s): Deutsche Forschungsgemeinschaft
- Award Id(s): 207786640 (Ki728/9-2)
- Funder(s):
- Award Group:
- Funder(s): EU Horizon 2020
- Award Id(s): 942937 (RENALTRACT)
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
- Split-screen
- Views Icon Views
- Open the PDF for in another window
-
Article Versions Icon
Versions
- Version of Record 17 February 2022
- Accepted Manuscript 28 January 2022
- Share Icon Share
-
Tools Icon
Tools
- Search Site
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 2022; dev.199735. doi: https://doi.org/10.1242/dev.199735
Download citation file:
Advertisement
Call for papers: Uncovering Developmental Diversity
Development invites you to submit your latest research to our upcoming special issue: Uncovering Developmental Diversity. This issue will be coordinated by our academic Editor Cassandra Extavour (Harvard University, USA) alongside two Guest Editors: Liam Dolan (Gregor Mendel Institute of Molecular Plant Biology, Austria) and Karen Sears (University of California Los Angeles, USA).
Choose Development in 2024
In this Editorial, Development Editor-in-Chief James Briscoe and Executive Editor Katherine Brown explain how you support your community by publishing in Development and how the journal champions serious science, community connections and progressive publishing.
Journal Meeting: From Stem Cells to Human Development
Register now for the 2024 Development Journal Meeting From Stem Cells to Human Development. Early-bird registration deadline: 3 May. Abstract submission deadline: 21 June.
Pluripotency of a founding field: rebranding developmental biology
This collaborative Perspective, the result of a workshop held in 2023, proposes a set of community actions to increase the visibility of the developmental biology field. The authors make recommendations for new funding streams, frameworks for collaborations and mechanisms by which members of the community can promote themselves and their research.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.