Wear and tear of the intestinal visceral musculature by intrinsic and extrinsic factors

Abstract

Background: The gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood.Results: Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as "sprout," "discontinuity," "furcation," and "crossover" of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissuedamaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well.Conclusions: Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.

Protocol to analyze Drosophila intestinal tumor cellular heterogeneity using immunofluorescence imaging and nuclear size quantification

“…Expression of oncogenes, such as an active form of Yorkie (Yki 3S/A ) and a mutant Ras (Ras V12 ), with esg ts induces intestinal tumors, which are marked by GFP ( Figure 1 A). 13 , 14 , 15 , 16 , 17 , 18 Notably, tumor cells induced by the expression of Yki 3S/A are quite variable in size, and a significant portion of them is even larger than normal ECs, suggesting their heterogeneity ( Figure 1 B).

Figure 1 Expression of yki 3S/A in ISCs and EBs induces intestinal hyperplasia (A) Representative images of esg ts > + and esg ts > yki 3S/A posterior midguts.

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