title: A suppressor/enhancer screen in Drosophila reveals a role for wnt-mediated lipid metabolism in primordial germ cell migration.
abstract: Wnt proteins comprise a large family of secreted ligands implicated in a wide variety of biological roles. WntD has previously been shown to inhibit the nuclear accumulation of Dorsal/NF-κB protein during embryonic dorsal/ventral patterning and the adult innate immune response, independent of the well-studied Armadillo/β-catenin pathway. In this paper, we present a novel phenotype for WntD mutant embryos, suggesting that this gene is involved in migration of primordial germ cells (PGC) to the embryonic gonad. Additionally, we describe a genetic suppressor/enhancer screen aimed at identifying genes required for WntD signal transduction, based on the previous observation that maternal overexpression of WntD results in lethally dorsalized embryos. Using an algorithm to narrow down our hits from the screen, we found two novel WntD signaling components: Fz4, a member of the Frizzled family, and the Drosophila Ceramide Kinase homolog, Dcerk. We show here that Dcerk and Dmulk (Drosophila Multi-substrate lipid kinase) redundantly mediate PGC migration. Our data are consistent with a model in which the activity of lipid phosphate phosphatases shapes a concentration gradient of ceramide-1-phosphate (C1P), the product of Dcerk, allowing proper PGC migration.
authors: Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Mark A
authors: MA
authors: McElwain
authors: Dennis C
authors: DC
authors: Ko
authors: Michael D
authors: MD
authors: Gordon
authors: Henrik
authors: H
authors: Fyrst
authors: Julie D
authors: JD
authors: Saba
authors: Roel
authors: R
authors: Nusse
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015139:Blotting, Southern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002518:Ceramides / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005260:Female; D005820:Genetic Testing; D005854:Germ Cells / Q000502:physiology*; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013489:Suppression, Genetic; D051176:beta Catenin / Q000378:metabolism
chemical_list: C522899:CERT protein, Drosophila; D002352:Carrier Proteins; D002518:Ceramides; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C504611:WntD protein, Drosophila; D051176:beta Catenin; C432152:frizzled protein 4, Drosophila