#nephrons

Not Responding

Our kidneys filter waste from our bloodstream, to be excreted as urine, thanks to units known as nephrons, where exchanges between blood in capillaries and fluid in renal tubules take place. During development, nephrons form from special progenitor cells (pictured in red, in a developing mouse kidney), a process dependent on proteins called R-spondins, which activate further signalling cascades. Without R-spondins, in mice, the multiplication, survival and differentiation of progenitor cells into nephron cells are strongly reduced, leading to a clear loss of nephrons. We have approximately one million nephrons per kidney on average, but numbers can vary widely between people, from 200,000 to over 2.5 million. Lower numbers have been linked to increased risk of chronic kidney disease, in which kidneys progressively lose their function; understanding the developmental causes behind this variation, including the role of R-spondins, could open up new perspectives for research into this condition.

Written by Emmanuelle Briolat

Image by Valerie P. I. Vidal and Andreas Schedl

Université Côte d’Azur, Inserm, CNRS, Institut de Biologie Valrose, Nice, France

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, April 2020

Making Connections

Macrophages are cells of the immune system, well known for engulfing and destroying pathogens or damaged cells, in a process called phagocytosis. Yet they also play a more constructive role during development, helping to build sophisticated networks in the kidneys. These organs regulate blood composition and filter out waste from the bloodstream to excrete as urine, thanks to a complex arrangement of carefully-structured minute tubules known as nephrons, closely associating with blood vessels. Pictured in a mouse embryo’s kidney, macrophages (in red) interact with blood vessels (in green) early on in development, helping to refine the position of kidney structures and encouraging connections between blood vessels. When macrophages were experimentally removed from developing kidneys, fewer connections formed. Understanding the role of macrophages may help produce more realistic kidney-mimicking organoids in the laboratory, for study and drug testing, and may even suggest future therapies targeting macrophages to treat kidney disease.

Written by Emmanuelle Briolat

Image from work by David A.D. Munro and colleagues

Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK

Image originally published under a Creative Commons Licence (BY 4.0)

Published in eLife, February 2019

Changing Identities

Where you grew up, where you moved to and where you live now have all shaped who you are. Cells are much the same, especially during development when they travel to their final destinations, exposing themselves to different microenvironments. Researchers investigate this process in kidney progenitor cells using sections of kidney tissue from mice (pictured). Some progenitor cells (white) mature into cells of the nephrons, the functional units of the kidney, while others maintain the pool of progenitors. The team fluorescently tagged Wnt4 (green), an early marker of maturing progenitor cells, which is switched on when these cells leave their ‘home’, where they normally reside in the kidney during development. They found through random cell movements, some of these cells returned home and were then able to switch off Wnt4. This highlights how flexible the identity of these cells is in response to the microenvironment they find themselves in.

Written by Lux Fatimathas

Image from work by Kynan T Lawlor and colleagues

Murdoch Children's Research Institute, Parkville, Victoria, Australia

Originally published under a Creative Commons Licence (BY 4.0)

Published in eLife, January 2019

More Nephrons Wnted

You’ve got around 2 million of them – nephrons, tiny filters in your kidneys that clear out the waste products in your blood. The right numbers of nephrons are produced during development by cells called nephron progenitors. A pool of these progenitors is maintained, with a steady stream maturing into different nephron cells. This fine balance is sustained by signalling molecules called Wnts. Researchers dig deeper by focusing on Wnt11, which accumulates at the tips of developing kidney branches where nephron progenitors live. Fluorescent imaging of kidneys from mutant mice lacking Wnt11 (pictured, right) revealed that the progenitors lost their sense of orientation, revealed by the polarised distribution of the protein desmin (green) within these cells being disrupted compared to normal kidneys (left). Mutants also depleted their pool of progenitors faster, resulting in half the number of nephrons and smaller kidneys. Wnt11 is therefore a major player in kidney development.

Written by Lux Fatimathas

Image from work by Lori L O'Brien and colleagues

Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Image originally published under a Creative Commons Licence (BY 4.0)

Published in eLife, December 2018

Brass Nephrons