Nephrocytes, the "storage kidneys" of Drosophila are highly reminiscent of mammalian podocytes. Transmission electron microscopy reveals the presence of a basal membrane and a slit diaphragm known from the mammalian filtration barrier. The structural similarities come along with a conserved molecular composition, as the core components of the slit diaphragm are the Neph-Nephrin homologues. We previously demonstrated that over-expression of endogenous Neph or Nephrin homologues lead to a gain of function phenotype resulting in nephrocyte fusion, defective filtration and reduced detoxification. Most importantly, this phenotype appears to depend on cytoplasmic signaling programs as Neph mutants lacking major parts of their cytoplasmic tail still localize correctly, but fail to induce correct nephrocyte fusion and filtration defects.
We utilize the nephrocytes as a platform to identify genes contributing to the slit diaphragm by an RNAi mediated suppressor screen and as a highly accessible model to study nephropathies.