Abstract: SA-PO0001
Exploring Neurovascular Crosstalk: Role of Vascular Smooth Muscle Cells in the Developing Kidneys
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Roetcisoender, Jake, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- N'Guetta, Pierre-Emmanuel, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- O'Brien, Lori L., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background
Kidney disease impacts around 1 in 7 adults in the US, with approximately 10% of the population worldwide estimated to be affected. There is a significant need for alternative regenerative strategies such as ex vivo tissue engineering that incorporate vascular and neural inputs as those historically haven't been included but remain a vital part of normal kidney homeostasis and function. To elucidate the role of the nerves and vasculature during kidney development, we utilized genetic mouse models and iDISCO+ tissue clearing with light-sheet microscopy to enable us to visualize these components in their native 3D architecture. The onset of kidney innervation coincides with arterial differentiation in mice, with nerves tightly associating with vascular smooth muscle cells (VSMCs). This association is maintained throughout development, as well as in mouse models of vascular mispatterning. When we genetically ablate the nerves, there is a reduction in nephron number illustrating the importance of innervation to proper kidney development. Thus, we hypothesize that VSMCs are essential for appropriate nerve guidance which is required for sufficient nephrogenesi
Methods
To interrogate the role of VSMCs during kidney development, we use SMC-specific and SMC progenitor Cre mice crossed with a diphtheria toxin allele mouse model to selectively ablate SMCs or their progenitors.
Results
Ablation of VSMCs after innervation is established appears to disrupt nerve patterning within the kidney. Ablation of VSMC progenitors interestingly leads to a significant reduction in innervation, with the majority of remaining nerve fibers innervating superficially as opposed to their normal internal innervation alongside vascular tracts.
Conclusion
Overall, this suggests an important role for VSMCs in facilitating proper nerve localization in the kidney both at early and later stages of development. Future experiments will continue using both VSMC and VSMC-progenitor ablation models to further characterize the role of these cells during kidney organogenesis and innervation.
Acknowledgment
R01DK121014 to LLO and T32HL069768 to JR. Pablo Ariel, PhD, in the UNC Microscopy Services Laboratory Core facility for imaging and analysis help.
Funding
- NIDDK Support