The journal Development published a special issue this week on organoids. Besides a wide variety of papers on organoid systems for different tissues, two papers are focusing on the developing kidney.
Since the demonstration by Unbekandt and Davies in 2010 that the classic Auerbach and Grobstein aggregation system could be adapted to only require cell types from the embryonic kidney itself, this aggregation method or derivatives from it have formed the basis of many seminal kidney organoid papers. However, the mechanism underlying this remarkable self-organization have remained unclear. Now Lefevre et al from the Little lab, using time-lapse and confocal imaging as well as mathematical modelling, study the dynamics of this reaggregation process.They use time-lapse imaging of reaggregated kidneys to study the kinetics of the spontaneous nephron initiation. Clusters of ureteric epithelium cells formed after 8 hours, which after 48 hours was followed by the formation of cap mesenchyme clusters around them. Mathematical modelling based on these time-lapse data suggested that at least in the first 24 hours differential adhesion between cells could account for the formation of the UE clusters. Finally, the authors hypothesise that homophilic cadherin interactions could explain this clustering, and using blocking antibodies they show that P-cadherin, but not E-cadherin, is likely involved in this clustering of UE cells in the first 24 hours. In all, this is a very interesting study on the mechanism behind these aggregation experiments.
A second kidney paper in this special issue is from the lab of Seppo Vainio. Saarela et al present a method to improve the confocal time-lapse imaging of kidney rudiments which they refer to as ‘fixed z-direction’ or ‘FiZD’ imaging. They limit the growth of the embryonic kidney in the z-direction by growing the kidney under a porous membrane but on a glass slide, with the two separated by glass beads that determine the space the growing kidney can get:
The system allows for very good development, including the formation of Loops of Henle, as had previously been observed in the Sebinger low-volume culture method. It would be interesting to see how these two different culture conditions allow this better development that the conventional method does not allow. The (confocal) imaging using the FiZD cultures is indeed superb and allows for computer-assisted cell segmentation and morphometric analysis. The FiZD system will no doubt find useful uses in the time-lapse and confocal imaging of developing kidneys.
Peter Hohenstein