Decreased expression of myogenic transcription factors and myosin heavy chains inCaenorhabditis elegansmuscles developed during spaceflight

Akira Higashibata,Noriaki Ishioka,Nathaniel J Szewczyk,Mari Imamizo-Sato,Catharine A Conley,Atsushi Higashitani

doi:10.1242/jeb.02365

Abstract

The molecular mechanisms underlying muscle atrophy during spaceflight are not well understood. We have analyzed the effects of a 10-day spaceflight on Caenorhabditis elegans muscle development. DNA microarray, real-time quantitative PCR, and quantitative western blot analyses revealed that the amount of MHC in both body-wall and pharyngeal muscle decrease in response to spaceflight. Decreased transcription of the body-wall myogenic transcription factor HLH-1 (CeMyoD) and of the three pharyngeal myogenic transcription factors, PEB-1, CEH-22 and PHA-4 were also observed. Upon return to Earth animals displayed reduced rates of movement, indicating a functional defect. These results demonstrate that C. elegans muscle development is altered in response to spaceflight. This altered development occurs at the level of gene transcription and was observed in the presence of innervation, not simply in isolated cells. This important finding coupled with past observations of decreased levels of the same myogenic transcription factions in vertebrates after spaceflight raises the possibility that altered muscle development is a contributing factor to spaceflight-induced muscle atrophy in vertebrates.

Highlights

The neuromuscular system is recognized as one of the physiologic systems most affected by spaceflight (Fitts et al, 2001)
Myogenesis appears to be controlled by the helix-loop-helix transcription factor HLH-1 (Chen et al, 1994; Krause, 1995), which controls the expression of two myosin heavy chain (MHC) isoforms [MHC A and B encoded by myo-3 and unc-54, respectively (Dibb et al, 1985; Epstein et al, 1974; Karn et al, 1983; MacLeod et al, 1981; Miller et al, 1986)]
In this report we demonstrate that muscles of C. elegans that developed in space, during the European Space Agency (ESA) DELTA mission, display decreased expression of the transcription factors controlling both body wall and pharyngeal muscle myogenesis as well as decreased expression of musclespecific MHCs

Summary

Introduction

The neuromuscular system is recognized as one of the physiologic systems most affected by spaceflight (Fitts et al, 2001). Myogenesis appears to be controlled by the helix-loop-helix transcription factor HLH-1 (Chen et al, 1994; Krause, 1995), which controls the expression of two MHC isoforms [MHC A and B encoded by myo-3 and unc-54, respectively (Dibb et al, 1985; Epstein et al, 1974; Karn et al, 1983; MacLeod et al, 1981; Miller et al, 1986)]. The pharyngeal muscles function rhythmically in feeding and possibly pseudocoelomic circulation They are analogous to vertebrate cardiac muscle, and contain two MHC isoforms [MHC C and D, encoded by myo-2 and myo-1, respectively (Ardizzi and Epstein, 1987; Miller et al, 1986)]. These MHCs appear to be regulated by the cooperative action of THE JOURNAL OF EXPERIMENTAL BIOLOGY

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