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

David Ad Munro, Yishay Wineberg, Julia Tarnick, Chris S. Vink, Zhuan Li, Clare Pridans, Elaine Dzierzak, Tomer Kalisky, Peter Hohenstein, Jamie A. Davies

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish
Article numbere43271
JournaleLife
Volume8
DOIs
StatePublished - Feb 2019

Bibliographical note

Publisher Copyright:
© Munro et al.

Funding

We would like to express our gratitude to Karen Chapman, Chris Mills, Clare Pridans, Samanta Mariani, Melanie Lawrence, and Jeremy Hughes for help and/or advice during the preparation of this work. We are also grateful to Anisha Kubasik-Thayil of the IMPACT imaging facility and Martin Waterfall of the Flow Cytometry Core Facility at the University of Edinburgh for their technical assistance. Thanks goes to Alison MacKinnon and Clare Pridans for sharing resources. This work was supported by the Medical Research Council (grant number: MR/K501293/1) and the Biotechnology and Biological Sciences Research Council (BBSRC; grant number BB/P013732/1).

FundersFunder number
Medical Research CouncilMR/K501293/1
Biotechnology and Biological Sciences Research CouncilBB/P013732/1

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