Physiology, Development, and Disease Modeling in the Drosophila Excretory System

Abstract

The insect excretory system contains two organ systems acting in concert: the Malpighian tubules and the hindgut perform essential roles in excretion and ionic and osmotic homeostasis. For over 350 years, these two organs have fascinated biologists as a model of organ structure and function. As part of a recent surge in interest, research on the Malpighian tubules and hindgut of Drosophila have uncovered important paradigms of organ physiology and development. Further, many human disease processes can be modeled in these organs. Here, focusing on discoveries in the past 10 years, we provide an overview of the anatomy and physiology of the Drosophila excretory system. We describe the major developmental events that build these organs during embryogenesis, remodel them during metamorphosis, and repair them following injury. Finally, we highlight the use of the Malpighian tubules and hindgut as accessible models of human disease biology. The Malpighian tubule is a particularly excellent model to study rapid fluid transport, neuroendocrine control of renal function, and modeling of numerous human renal conditions such as kidney stones, while the hindgut provides an outstanding model for processes such as the role of cell chirality in development, nonstem cell–based injury repair, cancer-promoting processes, and communication between the intestine and nervous system.

Cytoplasmic sharing through apical membrane remodeling

“…Each papilla is a polarized epithelial cone with the apical region facing the gut lumen and the basal region surrounding a central canal that connects to the fly’s hemolymph ( Figure 1D ). The papillar structure supports its function to reabsorb water, ions, and small molecules from the gut lumen and recycle them back to the hemolymph ( Cohen et al, 2020 ). Knowing that adult papillar cells share cytoplasm, we next used our dBrainbow system to identify when papillar cells begin to share relative to other developmental events that we previously identified ( Figure 1E ).…”

“…Finally, we tested whether cytoplasm sharing is essential for normal rectal papillar function. Rectal papillae selectively absorb water and ions from the gut lumen for transport back into the hemolymph, and excrete unwanted lumen contents ( Cohen et al, 2020 ). One test of papillar function is viability following the challenge of a high-salt diet ( Bretscher and Fox, 2016 ; Schoenfelder et al, 2014 ).…”

“…Here, we report a visual animal-wide screen, using multi-color lineage labeling approaches in the tractable animal model Drosophila melanogaster, for multinucleate tissues that share cytoplasm. We discover cytoplasm sharing in the rectal papilla, a common insect resorptive intestinal epithelium that is critical for maintaining ionic homeostasis ( Wigglesworth, 1932 ; Cohen et al, 2020 ). Likely due to its extreme proximal location in the gut of many insect species, this epithelium is linked to the infiltration of diverse pathogens, such as those involved in African sleeping sickness and also viruses being pursued as insect control measures ( Gu et al, 2010 ; Filosa et al, 2019 ).…”

Animal Models for Studying Stone Disease

“…Genetic studies of flies help identify potential candidate genes responsible for stone disease [ 72 ]. Cohen et al support using the Drosophila excretory system in order to study many human diseases [ 73 ]. They reviewed the anatomy and physiology of the fly’s Malphigian tubule, and proposed that the fly is an excellent model for studying many renal functions, renal stone diseases and cancer-promoting processes.…”

Accelerated cell cycles enable organ regeneration under developmental time constraints in theDrosophilahindgut

“…As documented by Robertson over 80 years ago (Robertson, 1936), the larval ileum undergoes histolysis, and is replaced by regenerative activity from adult hindgut precursors. Cell division from the larval pylorus, which occurs during metamorphosis, is the source of the expanded adult pylorus, and also the new adult ileum (Cohen et al, 2020;Fox and Spradling, 2009;Sawyer et al, 2017;Takashima et al, 2008;Yang and Deng, 2018). This development is not disrupted by a severe, acute injury to the wandering 3 rd instar larval pylorus.…”