Insulin-like signaling negatively regulates muscle arm extension through DAF-12 in Caenorhabditis elegans.
The body wall muscles (BWMs) of nematodes are connected to motor axons by muscle membrane extensions called muscle arms. To better understand how muscle arm extension is regulated, we screened conserved receptor tyrosine kinases for muscle arm defects in Caenorhabditis elegans. We discovered that mutations in daf-2, which encodes the only insulin-like receptor tyrosine kinase, confer a supernumerary muscle arm (Sna) phenotype. The Sna phenotype of daf-2 mutants is suppressed by loss-of-function in the canonical downstream FOXO-family transcription factor DAF-16 in either the muscles or the intestine, demonstrating that insulin-like signaling can regulate muscle arm extension non-autonomously. Furthermore, supernumerary arm extension requires the B isoform of the down-stream DAF-12 nuclear hormone receptor, which lacks the DNA-binding domain, but retains the ligand-binding domain. daf-2 regulates many processes in C. elegans including entry into dauer, which is a diapause-like state that facilitates survival of harsh environmental conditions. We found that wild-type dauers are also Sna. Unlike other changes associated with dauer, however, the Sna phenotype of dauers persists in recovered adults. Finally, disruption of a TGF-beta pathway that regulates dauer formation in parallel to the insulin-like pathway also confers the Sna phenotype. We conclude that supernumerary muscle arms are a novel dauer-specific modification that may facilitate some aspect of dauer behavior.
Dixon
Scott J
SJ
Department of Molecular Genetics, Collaborative Program in Developmental Biology, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1.
Alexander
Mariam
M
Chan
Kevin Ka Ming
KK
Roy
Peter John
PJ
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007422:Intestines / Q000033:anatomy & histology / Q000502:physiology; D009132:Muscles / Q000033:anatomy & histology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; C116661:DAF-18 protein, C elegans; D007328:Insulin; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin