SDN-1/syndecan regulates growth factor signaling in distal tip cell migrations in C. elegans.
Mutations in the sdn-1/syndecan gene act as genetic enhancers of the ventral-to-dorsal distal tip cell (DTC) migration defects caused by a weak allele of the netrin receptor gene unc-5. The sdn-1(ev697) allele was identified in a genetic screen for enhancers of unc-5 DTC migration defects, and carried a nonsense mutation predicted to truncate the SDN-1 protein prior to the transmembrane domain. The enhancement of unc-5 caused by an sdn-1 mutation was rescued by expression of wild-type sdn-1 in the hypodermis or nervous system rather than the DTCs, indicating a cell non-autonomous function of sdn-1. The enhancement was also partially reversed by mutations in the egl-17/FGF or egl-20/Wnt genes, suggesting that sdn-1 affects UNC-5 function through a mis-regulation of signaling in growth factor pathways. egl-20 reporter constructs exhibited increased and mis-localized EGL-20 distribution in sdn-1 mutants compared to wild-type animals. Finally, using loss of function mutations, we show that egl-17/Fgf and egl-20/Wnt are partially redundant in regulating the migration pattern of the posterior DTC, as double mutants exhibit significant frequencies of defects in migration phases along both the anteroposterior and dorsoventral axes. Together these results suggest that SDN-1 affects UNC-5 function by regulating the proper extracellular distribution of growth factors.
Schwabiuk
Megan
M
Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E J73.
Coudiere
Ludivine
L
Merz
David C
DC
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053667:Syndecans / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D051153:Wnt Proteins; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C105157:Egl-17 protein, C elegans; C117259:Egl-20 protein, C elegans; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D053667:Syndecans; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C077588:UNC-5 protein, C elegans