Abstract
Biology is adapted to Earth’s gravity force, and the long-term effects of varying gravity on the development of animals is unclear. Previously, we reported that high gravity, called hypergravity, increases defects in the development of motor neuron axons in the nematode Caenorhabditis elegans. Here, we show that a mutation in the unc-70 gene that encodes the cytoskeletal β-spectrin protein suppresses hypergravity-induced axon defects. UNC-70 expression is required in both muscle and epidermis to promote the axon defects in high gravity. We reveal that the location of axon defects is correlated to the size of the muscle cell that the axon traverses. We also show that mutations that compromise key proteins of hemidesmosomal structures suppress hypergravity-induced axon defects. These hemidesmosomal structures play a crucial role in coupling mechanical force between the muscle, epidermis and the external cuticle. We speculate a model in which the rigid organization of muscle, epidermal and cuticular layers under high gravity pressure compresses the narrow axon migration pathways in the extracellular matrix hindering proper axon pathfinding of motor neurons.
Highlights
Organisms and biological systems constantly adapt to and evolve with their changing environments
We showed that hypergravity exposure increases DD/VD motor neuron axon d efects[22]
We showed that hypergravity exposure increases DD/VD motor neuron axon defects[22]
Summary
Organisms and biological systems constantly adapt to and evolve with their changing environments. Studies of C. elegans in space have verified that microgravity lowers the expression of muscle development transcription factors to decrease muscle d evelopment[13], alters TGF-β expression to decrease growth of body length[14,15] and alters fat-related genes and results in decreased accumulation of fat. Β-spectrin protein is known to play roles in the structure of both neurons and muscle, and we find that muscle size is correlated with DD/VD axon defects, our results show that UNC-70 expression in both the epidermis and muscle together promotes hypergravity-induced axon defects. This is supported by genetic analysis of molecules expressed in muscle, ECM, epidermis and the cuticle. Our results promote a model in which proteins that support the proper layered structure of muscle, epidermis and cuticle can become a hindrance in a high gravity force environment
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