Abstract
Genetic mechanisms for the pathogenesis of visceral myopathy (VM) have been rarely demonstrated. Here we report the visceral role of misato (mst) in Drosophila and its implications for the pathogenesis of VM. Depletion of mst using three independent RNAi lines expressed by a pan-muscular driver elicited characteristic symptoms of VM, such as abnormal dilation of intestinal tracts, reduced gut motility, feeding defects, and decreased life span. By contrast, exaggerated expression of mst reduced intestine diameters, but increased intestinal motilities along with thickened muscle fibers, demonstrating a critical role of mst in the visceral muscle. Mst expression was detected in the adult intestine with its prominent localization to actin filaments and was required for maintenance of intestinal tubulin and actomyosin structures. Consistent with the subcellular localization of Mst, the intestinal defects induced by mst depletion were dramatically rescued by exogenous expression of an actin member. Upon ageing the intestinal defects were deteriorative with marked increase of apoptotic responses in the visceral muscle. Taken together, we propose the impairment of actomyosin structures induced by mst depletion in the visceral muscle as a pathogenic mechanism for VM.
Highlights
Genetic mechanisms for the pathogenesis of visceral myopathy (VM) have been rarely demonstrated
To examine whether the intestinal phenotype is due to any developmental defects by mst depletion, we restricted the mst knockdown in the adulthood using the temperature sensitive GAL80 combined with mef2-GAL4 to induce expression of mst RNAi in the muscle only after birth at the non-permissive temperature (30 °C)
We observed that mst knockdown in the adult still produced dilation of the intestine (Fig. S1B). Along with this intestinal phenotype, we observed that mef2 > mst RNAi flies showed less frequent contraction of the intestine, shortened life span, increased gut permeability, and elevated infection compared to controls (Figs 1E and F, S1C, and D, respectively), indicating mst depletion affected intestinal morphology and intestinal homeostasis
Summary
Genetic mechanisms for the pathogenesis of visceral myopathy (VM) have been rarely demonstrated. Extensive studies using Drosophila have been performed to reveal how visceral muscle contributes to the cellular homeostasis in the intestine including regulation of intestinal stem cells by visceral muscle-derived factors such as Wingless/Wnt and epidermal growth factor[15,16]. Besides these anatomical conservations, a plenty of genetic tools are available[17]. An investigation on patients with inflammatory bowel disease revealed an SNP on the locus 1q22 containing MSTO124
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