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Netrin 1 directs vascular patterning and maturity in the developing kidney.

Samuel E Honeycutt1, Pierre-Emmanuel Y N'Guetta1, Deanna M Hardesty1

  • 1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Development (Cambridge, England)
|October 11, 2023
PubMed
Summary

Netrin 1 (Ntn1), a key guidance signal, is crucial for kidney vascular development. Its absence in Foxd1+ stromal cells leads to hypoplastic kidneys with abnormal vascular patterns and reduced arterialization.

Keywords:
Kidney developmentMouseNetrin 1PatterningSignalingStromaVasculature

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Area of Science:

  • Developmental Biology
  • Renal Physiology
  • Vascular Biology

Background:

  • Kidney vascular architecture is vital for homeostasis but poorly understood.
  • Kidney signals influencing vessel maturity and patterning require further investigation.
  • Netrin 1 (Ntn1) is a known guidance ligand for vessels and neurons.

Purpose of the Study:

  • To investigate the role of Netrin 1 (Ntn1) in kidney vascular development.
  • To determine how Ntn1, expressed by Foxd1+ stromal progenitors, affects kidney vascular architecture and maturity.

Main Methods:

  • Conditional deletion of Ntn1 in Foxd1+ kidney stromal progenitors in mice.
  • Whole-mount 3D imaging for vascular pattern analysis.
  • Immunohistochemistry for endothelial and smooth muscle markers.
  • Whole kidney RNA-sequencing.

Main Results:

  • Conditional deletion of Ntn1 resulted in hypoplastic kidneys with disrupted vascular patterning.
  • Reduced arterial smooth muscle metrics were observed in mutant kidneys.
  • RNA-seq revealed dysregulation of genes related to stromal cells, vasculature, and nephron differentiation.

Conclusions:

  • Ntn1 signaling from kidney stromal progenitors is essential for proper vascular development and patterning.
  • Ntn1 influences kidney vascular maturity, specifically arterialization.
  • These findings underscore Ntn1's critical role in kidney development and vascularization.