Fluid dynamics alter Caenorhabditis elegans body length via neuromuscular signaling with TGF-β/DBL-1
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Skeletal muscle wasting is a major obstacle for long-term space exploration. Similar to astronauts, the nematode Caenorhabditis elegans displays negative muscular and physical effects grown in space microgravity. However, it is still unclear what signal molecules and behavior affect the negative alterations. We here studied key signaling molecules involved in alterations of C. elegans physique in response to fluid-dynamics on the ground-based experiments. Like as spaceflight experiment with 1G accelerator onboard, a myosin heavy chain myo-3 and a TGF- dbl-1 gene expression altered increasing the fluid dynamic parameters viscosity/drag resistance or depth of liquid culture. These gene expression also drastically increased grown liquid medium as compared with moist agar surface. In addition, body length enhanced in WT and body-wall cuticle collagen mutants, rol-6 roller and dpy-5 dumpy, grown in liquid culture. On the other hand, in a TGF- gene dbl-1 and its signaling pathway sma-4/Smad mutants, their body lengths did not alter in liquid. Similarly, a D1-like dopamine receptor DOP-4 and a mechanosensory channel UNC-8 were required for altered physique in which DBL-1 signaling did not upregulated in liquid. Since C. elegans contraction rates are much higher in swimming mode in liquid than clawing mode on agar surface, we studied the relationship between body-length enhancement and contraction rate. Mutants significantly reduced contraction rate commonly show smaller size, although the rate in dop-4, dbl-1 and sma-4 mutants still increased in liquid. These results suggest that neuromuscular signaling via TGF-/DBL-1 to alter body physique in response to environmental conditions including fluid dynamics.
We are grateful to the entire crew of the CERISE for their work on STS-129, STS-130, and the International Space Station. The CERISE was organized with the support of the JAXA. We also thank the Caenorhabditis elegans Genetic Center for kindly supplying the mutant strains. This work was also supported by JSPS KAKENHI grant numbers 26506029, 15H05937, the Cross-ministerial Strategic Innovation Promotion Program (J150000592), the Medical Research Council UK (G0801271), and National Institutes of Health (NIH NIAMS ARO54342). This work was supported by grants from the MEXT, the JSPS (15H05937, 26506029), the Cross-ministerial Strategic Innovation Promotion Program (J150000592), and the Cell Biology Experiment Project conducted by the Institute of Space and Astronautical Science in JAXA. TE was supported by the Medical Research Council of UK (G0801271). NJS was supported by the National Institutes of Health (NIH NIAMS ARO54342).
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Vol. 2, article 16006