Insights into human kidney function from the study of Drosophila

Abstract

Biological and biomedical research using Drosophila melanogaster as a model organism has gained recognition through several Nobel prizes within the last 100 years. Drosophila exhibits several advantages when compared to other in vivo models such as mice and rats, as its life cycle is very short, animal maintenance is easy and inexpensive and a huge variety of transgenic strains and tools are publicly available. Moreover, more than 70% of human disease-causing genes are highly conserved in the fruit fly. Here, we explain the use of Drosophila in nephrology research and describe two kidney tissues, Malpighian tubules and the nephrocytes. The latter are the homologous cells to mammalian glomerular podocytes and helped to provide insights into a variety of signaling pathways due to the high morphological similarities and the conserved molecular make-up between nephrocytes and podocytes. In recent years, nephrocytes have also been used to study inter-organ communication as links between nephrocytes and the heart, the immune system and the muscles have been described. In addition, other tissues such as the eye and the reproductive system can be used to study the functional role of proteins being part of the kidney filtration barrier.

A genetic and physiological model of renal dysfunction in Lowe syndrome

“…Nephrocytes uptake hemolymph by endocytosis, sort the endocytosed cargo for degradation in lysosomes or recycle it back to the cell surface. This endocytic function is like that seen in proximal tubular cells and hence offers avenues to model various aspects of proximal tubular functions (Helmstädter et al, 2017) (Koehler and Huber, 2023). Owing to their large size, nephrocytes allow both live cell imaging of organelle structure, function, and analysis of physiological readouts from intact animals.…”

“…Moreover, it is well established that the receptors cubilin and amnionless are required for reabsorption of proteins via proximal tubular cells. The presence of cubilin and amnionless exclusively on Drosophila nephrocytes and their conserved function in protein uptake suggests evolutionary conservation between these cell types (Koehler and Huber, 2023). Therefore, Drosophila nephrocytes can provide insights into the proximal tubular dysfunction observed in LS.…”

Developmental and Nutritional Dynamics of Malpighian Tubule Autofluorescence in the Asian Tiger Mosquito Aedes albopictus

“…The advantages lie in the easy and cost-effective insect rearing, the availability of suitable genetic mutants or transgenic strains and the exemption of experiments involving insects from ethical standards governing the use of animals for scientific purposes [ 8 , 9 , 10 ]. One such example is the study of Drosophila melanogaster (Diptera: Drosophilidae) MTs as a model for investigating the etiology of kidney crystal formation, exploring possible pharmacological treatments for stone disease [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Phospholipid scramblase 1: an essential component of the nephrocyte slit diaphragm

“…The entire nephrocyte surface contains deep membrane invaginations -the labyrinthine channels-that are sealed from the surrounding hemolymph by SDs, which are arranged in long strands depicting a fingerprint-like pattern. Sticks and stones (Sns) and Dumbfounded (Duf, also referred as Kin of irre, Kirre), orthologs to nephrin and NEPH1 respectively, interact through their extracellular domains to form these junctions [10][11][12][13].…”