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Fluid dynamics alter Caenorhabditis elegans body length via TGF-?/DBL-1 neuromuscular signaling

Harada, Shunsuke; Hashizume, Toko; Nemoto, Kanako; Shao, Zhenhua; Higashitani, Nahoko; Etheridge, Timothy; Szewczyk, Nathaniel J.; Fukui, Keiji; Higashibata, Akira; Higashitani, Atsushi


Shunsuke Harada

Toko Hashizume

Kanako Nemoto

Zhenhua Shao

Nahoko Higashitani

Timothy Etheridge

Nathaniel J. Szewczyk

Keiji Fukui

Akira Higashibata

Atsushi Higashitani


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-? (TGF-?), 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-?, 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-?/DBL-1 acts to alter body physique in response to environmental conditions including fluid dynamics.


Harada, S., Hashizume, T., Nemoto, K., Shao, Z., Higashitani, N., Etheridge, T., …Higashitani, A. (2016). Fluid dynamics alter Caenorhabditis elegans body length via TGF-β/DBL-1 neuromuscular signaling. npj Microgravity, 2(1), Article 16006.

Journal Article Type Article
Acceptance Date Jan 10, 2016
Online Publication Date Apr 7, 2016
Publication Date Dec 1, 2016
Deposit Date Nov 20, 2018
Publicly Available Date Jan 17, 2019
Journal npj Microgravity
Print ISSN 2373-8065
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 2
Issue 1
Article Number 16006
Public URL
Publisher URL


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