Nephrocytes are part of the spectrum of filtration epithelial diversity

Abstract

The excretory system produces urine by ultrafiltration via a filtration epithelium. Podocytes are widely found as filtration epithelial cells in eucoelomates. In some animal taxa, including insects and crustaceans, nephrocytes serve to separate toxic substances from the body fluid, in addition to podocytes. Drosophila nephrocytes have been recently utilized as a model system to study podocyte function and disease. However, functionality and cellular architecture are strikingly different between Drosophila nephrocytes and eucoelomate podocytes, and the phylogenetic relationship between these cells remains enigmatic. In this study, using focused-ion beam-scanning electron microscopy (FIB-SEM) tomography, we revealed three-dimensional architecture of decapod nephrocytes with unprecedented accuracy—they filled an enormous gap, which can be called “missing link,” in the evolutionary diversity of podocytes and nephrocytes. Thus, we concluded that nephrocytes are part of the spectrum of filtration epithelial diversity in animal phylogeny.

Molecular evidence for a single origin of ultrafiltration-based excretory organs

“…Besides Malpighian tubules, insects also possess specialized excretory cells-nephrocytes-that perform an ultrafiltration-like process with a filter composed of Nephrin, KIRREL, and ZO1. 64 The presence of this conserved UF apparatus as well as the morphological data from crustaceans, in which nephrocytes develop from metanephridial podocytes 65 and forms intermediate between both cell types are known, 66 indicate that the ancestral UFbased organs of insects might became reduced to single excretory cells, 16 in tandem with the development of Malpighian tubules. Further investigation of the molecular basis of the development of Malpighian tubules and H-system in additional, non-model arthropod and nematode species is needed in order to understand how the ancestral UF-based organs got replaced by entirely new excretory systems in those two evolutionarily successful groups.…”

Three-Dimensional Architecture of Glomerular Endothelial Cells Revealed by FIB-SEM Tomography

“…Focused-ion beam-SEM tomography with a 3D reconstruction technique is a powerful approach used in our previous podocyte research ( Ichimura et al, 2015 , 2017 , 2019 ; Kawasaki et al, 2019 ; Miyaki et al, 2020c ). In the present study, we clearly visualized the 3D cytoarchitecture of normal GEnCs in adult rats.…”

“…Moreover, three-dimensional (3D) cellular structures can be reconstructed from serial sectional images with high reliability ( Miyaki et al, 2020a , b ). Recently, using this approach, our group has re-evaluated the 3D ultrastructure of podocytes in the context of health ( Ichimura et al, 2015 ), development ( Ichimura et al, 2017 ), disease ( Ichimura et al, 2019 ), and evolution ( Ichimura and Sakai, 2017 ; Kawasaki et al, 2019 ; Miyaki et al, 2020c ). The 3D reconstructed images of single podocytes enable the evaluation of surface structures of these cells from any direction and without interference by neighboring podocytes and the GBM.…”

The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes

“…Due to the high similarity between nephrocytes and mammalian glomerular podocytes, Drosophila is an appropriate model system for studying podocyte biology in vivo. The primary constituents of the slit diaphragm in Drosophila melanogaster, including nephrin, podocin, and related proteins, are expressed in nephrocytes to filter and detoxify hemolymph [7].…”

“…Nephrocytes efficiently pick up secreted fluorescent proteins, indicating that they have no involvement in primary urine generation, but rather function to endocytose hazardous compounds from the hemolymph [7]. The GAL4-UAS system is a highly effective genetic tool for studying Drosophila gene expression and function.…”