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Kidney Week

Abstract: PO0639

Interrogating the Contribution of Innervation to Kidney Development and Disease

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • 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

Group or Team Name

  • O'Brien Lab
Background

Kidney functions range from blood filtration and regulation of body fluid homeostasis to promoting the production of red blood cells and active vitamin D. These functions are regulated by intrinsic cellular mechanisms including signaling through renal nerves. The kidney is innervated by axonal projections from exterior ganglia. These projections can be classified as either afferent sensory fibers which impact cardiovascular function by relaying information from the kidney to the central nervous system (CNS), or efferent sympathetic fibers which impact renal function by relaying information from the CNS to the kidney. While the role of innervation in adult renal pathophysiology is an area of active investigation, there is a significant deficit in our understanding of renal innervation during development. I hypothesize that renal nerves release spatially and temporally regulated signaling factors contributing to proper kidney development.

Methods

To first characterize the process of renal innervation, we generated 3D anatomical maps of renal innervation throughout development using light-sheet imaging of embryonic, neonatal, and adult kidneys. We also utilized confocal microscopy to interrogate the association of renal nerves (synapse formation) with distinct renal structures including tubules, glomeruli, and vasculature. To assess function, we genetically ablated renal innervation utilizing a knockout mouse for the TrkA receptor which is required for neuronal survival.

Results

Our analyses show that renal innervation begins at E13.5 as the renal arterial tree becomes smooth muscle actin (SMA) coated. Innervation continues via multiple branching events following SMA+ vasculature until the main renal nerve branches are established by E16.5. From there, renal nerves grow further via interstitial branching until projections reach renal target structures as early as E17.5. TrkA knockout kidneys assessed postnatally had a significant reduction in renal innervation and presented with abnormal glomerular and tubules phenotypes.

Conclusion

Future efforts will aim to conditionally delete sensory or sympathetic renal nerves independently and investigate the resulting functional phenotypes. Taken together our findings will significantly bridge the gap in knowledge concerning the establishment of renal innervation and the role of nerves in kidney development and disease.