TY - JOUR
T1 - Fluid dynamics alter caenorhabditis elegans body length via TGF-β/DBL-1 neuromuscular signaling
AU - Harada, Shunsuke
AU - Hashizume, Toko
AU - Nemoto, Kanako
AU - Shao, Zhenhua
AU - Higashitani, Nahoko
AU - Etheridge, Timothy
AU - Szewczyk, Nathaniel J.
AU - Fukui, Keiji
AU - Higashibata, Akira
AU - Higashitani, Atsushi
N1 - Funding Information:
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).
Publisher Copyright:
© 2016 Macmillan Publishers Limited.
PY - 2016/1/7
Y1 - 2016/1/7
N2 - 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 when in microgravity in space. It remains unclear what signaling molecules and behavior(s) cause these negative alterations. Here we studied key signaling molecules involved in alterations of C. elegans physique in response to fluid dynamics in ground-based experiments. Placing worms in space on a 1G accelerator increased a myosin heavy chain, myo-3, and a transforming growth factor-β (TGF-β), dbl-1, gene expression. These changes also occurred when the fluid dynamic parameters viscosity/drag resistance or depth of liquid culture were increased on the ground. In addition, body length increased in wild type and body wall cuticle collagen mutants, rol-6 and dpy-5, grown in liquid culture. In contrast, body length did not increase in TGF-β, dbl-1, or downstream signaling pathway, sma-4/Smad, mutants. Similarly, a D1-like dopamine receptor, DOP-4, and a mechanosensory channel, UNC-8, were required for increased dbl-1 expression and altered physique in liquid culture. As C. elegans contraction rates are much higher when swimming in liquid than when crawling on an agar surface, we also examined the relationship between body length enhancement and rate of contraction. Mutants with significantly reduced contraction rates were typically smaller. However, in dop-4, dbl-1, and sma-4 mutants, contraction rates still increased in liquid. These results suggest that neuromuscular signaling via TGF-β/DBL-1 acts to alter body physique in response to environmental conditions including fluid dynamics.
AB - 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 when in microgravity in space. It remains unclear what signaling molecules and behavior(s) cause these negative alterations. Here we studied key signaling molecules involved in alterations of C. elegans physique in response to fluid dynamics in ground-based experiments. Placing worms in space on a 1G accelerator increased a myosin heavy chain, myo-3, and a transforming growth factor-β (TGF-β), dbl-1, gene expression. These changes also occurred when the fluid dynamic parameters viscosity/drag resistance or depth of liquid culture were increased on the ground. In addition, body length increased in wild type and body wall cuticle collagen mutants, rol-6 and dpy-5, grown in liquid culture. In contrast, body length did not increase in TGF-β, dbl-1, or downstream signaling pathway, sma-4/Smad, mutants. Similarly, a D1-like dopamine receptor, DOP-4, and a mechanosensory channel, UNC-8, were required for increased dbl-1 expression and altered physique in liquid culture. As C. elegans contraction rates are much higher when swimming in liquid than when crawling on an agar surface, we also examined the relationship between body length enhancement and rate of contraction. Mutants with significantly reduced contraction rates were typically smaller. However, in dop-4, dbl-1, and sma-4 mutants, contraction rates still increased in liquid. These results suggest that neuromuscular signaling via TGF-β/DBL-1 acts to alter body physique in response to environmental conditions including fluid dynamics.
UR - http://www.scopus.com/inward/record.url?scp=85052593353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052593353&partnerID=8YFLogxK
U2 - 10.1038/npjmgrav.2016.6
DO - 10.1038/npjmgrav.2016.6
M3 - Article
AN - SCOPUS:85052593353
VL - 2
JO - npj Microgravity
JF - npj Microgravity
SN - 2373-8065
M1 - 16006
ER -