FGF negatively regulates muscle membrane extension in Caenorhabditis elegans.
Striated muscles from Drosophila and several vertebrates extend plasma membrane to facilitate the formation of the neuromuscular junction (NMJ) during development. However, the regulation of these membrane extensions is poorly understood. In C. elegans, the body wall muscles (BWMs) also have plasma membrane extensions called muscle arms that are guided to the motor axons where they form the postsynaptic element of the NMJ. To investigate the regulation of muscle membrane extension, we screened 871 genes by RNAi for ectopic muscle membrane extensions (EMEs) in C. elegans. We discovered that an FGF pathway, including let-756(FGF), egl-15(FGF receptor), sem-5(GRB2) and other genes negatively regulates plasma membrane extension from muscles. Although compromised FGF pathway activity results in EMEs, hyperactivity of the pathway disrupts larval muscle arm extension, a phenotype we call muscle arm extension defective or MAD. We show that expression of egl-15 and sem-5 in the BWMs are each necessary and sufficient to prevent EMEs. Furthermore, we demonstrate that let-756 expression from any one of several tissues can rescue the EMEs of let-756 mutants, suggesting that LET-756 does not guide muscle membrane extensions. Our screen also revealed that loss-of-function in laminin and integrin components results in both MADs and EMEs, the latter of which are suppressed by hyperactive FGF signaling. Our data are consistent with a model in which integrins and laminins are needed for directed muscle arm extension to the nerve cords, while FGF signaling provides a general mechanism to regulate muscle membrane extension.
Dixon
Scott J
SJ
Department of Medical Genetics and Microbiology, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 1A, Canada.
Alexander
Mariam
M
Fernandes
Raynah
R
Ricker
Nicole
N
Roy
Peter J
PJ
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000502:physiology*; D004625:Embryo, Nonmammalian; D005109:Extracellular Matrix / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D007700:Kinetics; D007814:Larva; D008954:Models, Biological; D009132:Muscles / Q000196:embryology* / Q000502:physiology; D009154:Mutation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D013696:Temperature
D029742:Caenorhabditis elegans Proteins; D005346:Fibroblast Growth Factors