Hypergravity hinders axonal development of motor neurons in Caenorhabditis elegans

Abstract

As space flight become more accessible in the future, humans will be exposed to gravity conditions other than our 1G environment on Earth. Changes in physiology and anatomy in altered gravity conditions have long been observed, especially the loss of muscle mass during long-term space habitation, the reason for which is not fully understood. Although much effort has gone into studying the effects of gravity in muscle physiology, its effect on the development of neurons has not been thoroughly assessed. Using the nematode model organism Caenorhabditis elegans, we examined changes in response to hypergravity in the development of the 19 GABAergic DD/VD motor neurons that innervate body muscle.We found that a high gravity force above 10G significantly increases the number of animals with defects in the development of axonal projections from the DD/VD neurons.We showed that a critical period of hypergravity exposure during the embryonic/early larval stage was sufficient to induce defects. While characterizing the nature of the axonal defects, we found that in normal 1G gravity conditions, DD/VD axonal defects occasionally occurred, with the majority of defects occurring on the dorsal side of the animal and in the mid-body region, and a significantly higher rate of error in the 13 VD axons than the 6 DD axons. Hypergravity exposure increased the rate of DD/VD axonal defects, but did not change the distribution or the characteristics of the defects. Our study demonstrates that in addition to gravity's effects on muscle development, gravity can also impact motor neuron development. 16 As space flight become more accessible in the future, humans will be exposed to gravity 17 conditions other than our 1G environment on Earth. Changes in physiology and anatomy in 18 altered gravity conditions have long been observed, especially the loss of muscle mass during 19 long-term space habitation, the reason for which is not fully understood. Although much effort 20 has gone into studying the effects of gravity in muscle physiology, its effect on the development 21 of neurons has not been thoroughly assessed. Using the nematode model organism 22 Caenorhabditis elegans, we examined changes in response to hypergravity in the development of 23 the 19 GABAergic DD/VD motor neurons that innervate body muscle. We found that a high 24 gravity force above 10G significantly increases the number of animals with defects in the 25 development of axonal projections from the DD/VD neurons. We showed that a critical period of 26 hypergravity exposure during the embryonic/early larval stage was sufficient to induce defects.27 While characterizing the nature of the axonal defects, we found that in normal 1G gravity 28 conditions, DD/VD axonal defects occasionally occurred, with the majority of defects occurring 29 on the dorsal side of the animal and in the mid-body region, and a significantly higher rate of 30 error in the 13 VD axons than the 6 DD axons. Hypergravity exposure increased the rate of 31 DD/VD axonal defects, but did not change t...

Mechanosensory Systems and Sensory Integration Mediate C. elegans Negative Gravitaxis

“…While little is known about their behavioral responses to gravity, the effects of hyper-and microgravity on C. elegans physiology has been documented [23][24][25][26][27] . In response to hypergravitational forces, signaling by the mechanosensory DEG/ENaC sodium channel proteins, MEC-4/MEC-10, leads to nuclear localization of the DAF-16 FoxO transcription factor, which also transduces insulin-like growth factor signaling and stress responses 28 .…”