Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development

Elife. 2019 Feb 13:8:e43271. doi: 10.7554/eLife.43271.

Abstract

The origins and functions of kidney macrophages in the adult have been explored, but their roles during development remain largely unknown. Here we characterise macrophage arrival, localisation, heterogeneity, and functions during kidney organogenesis. Using genetic approaches to ablate macrophages, we identify a role for macrophages in nephron progenitor cell clearance as mouse kidney development begins. Throughout renal organogenesis, most kidney macrophages are perivascular and express F4/80 and CD206. These macrophages are enriched for mRNAs linked to developmental processes, such as blood vessel morphogenesis. Using antibody-mediated macrophage-depletion, we show macrophages support vascular anastomoses in cultured kidney explants. We also characterise a subpopulation of galectin-3+ (Gal3+) myeloid cells within the developing kidney. Our findings may stimulate research into macrophage-based therapies for renal developmental abnormalities and have implications for the generation of bioengineered kidney tissues.

Keywords: blood vessel; cell migration; developmental biology; human; morphogenesis; mouse; nephron; phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Cell Lineage / genetics
  • Galectin 3 / genetics*
  • Gene Expression Regulation, Developmental
  • Kidney / growth & development*
  • Kidney / metabolism
  • Lectins, C-Type / genetics
  • Macrophages / metabolism
  • Mannose Receptor
  • Mannose-Binding Lectins / genetics
  • Mice
  • Nephrons / growth & development*
  • Nephrons / metabolism
  • Organogenesis / genetics*
  • Receptors, Cell Surface / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Stem Cells / metabolism

Substances

  • Adgre1 protein, mouse
  • Calcium-Binding Proteins
  • Galectin 3
  • Lectins, C-Type
  • Lgals3 protein, mouse
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled