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Abstract: SA-OR19

Establishing the Spatiotemporal Organization and Function of Renal Nerves Throughout Nephrogenesis

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 Department of Cell Biology and Physiology, Chapel Hill, North Carolina, United States
  • O'Brien, Lori L., The University of North Carolina at Chapel Hill Department of Cell Biology and Physiology, Chapel Hill, North Carolina, United States

Group or Team Name

  • O'Brien Lab
Background

Essential kidney functions are regulated by intrinsic cellular mechanisms including signaling through renal nerves. Despite their significance to renal physiology, we still lack a fundamental understanding of the establishment, organization, and function of kidney innervation during organogenesis. Our goal is to spatially and temporally map renal sensory and sympathetic innervation throughout development to identify cellular targets and elucidate functional crosstalk.

Methods

To assess the process of kidney innervation across development, we generated 3D anatomical maps of renal nerves using light-sheet fluorescent microscopy and confocal microscopy.

Results

Our analyses show that renal innervation initiates at E13.5 as these nerves track closely with the smooth muscle-coated arterial tree. We find that sensory and sympathetic nerves innervate the kidney concomitantly, and that innervation continues via branching events as axons track with the developing vasculature. After the establishment of the renal neurovascular main branches, we observed subsequent interstitial branching by E17.5 as renal nerves grow until axonal projections reach their targets. Further, we uncovered that renal nerves synapse with the vasculature as early as E16.5, suggesting the establishment of functional crosstalk. We also observed synapses near glomeruli and tubules by E18.5. To assess functional roles for nerves during kidney development, we genetically ablated neurons innervating the kidney utilizing a TrkA knockout mouse. Postnatal TrkA knockout kidneys had a significant reduction in renal innervation and presented with reduced glomerular number and dilated proximal tubules, suggesting renal nerves mediate proper nephrogenesis and/or early function.

Conclusion

Taken together our findings provide novel insights into the establishment of renal innervation and the role renal nerves play during development. Future efforts will aim to conditionally delete sensory or sympathetic renal nerves independently and investigate the developmental and functional phenotypes.

Funding

  • NIDDK Support