RRC ID 15395
著者 McElwain MA, Ko DC, Gordon MD, Fyrst H, Saba JD, Nusse R.
タイトル A suppressor/enhancer screen in Drosophila reveals a role for wnt-mediated lipid metabolism in primordial germ cell migration.
ジャーナル PLoS One
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.
巻・号 6(11)
ページ e26993
公開日 2011-11-1
DOI 10.1371/journal.pone.0026993
PII PONE-D-11-16121
PMID 22069480
PMC PMC3206050
MeSH Animals Animals, Genetically Modified Blotting, Southern Blotting, Western Carrier Proteins / genetics Carrier Proteins / metabolism Cell Movement* Ceramides / metabolism Drosophila / genetics* Drosophila / growth & development Drosophila / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism Enhancer Elements, Genetic Female Genetic Testing* Germ Cells / physiology* Immunoprecipitation Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Lipid Metabolism Male Phylogeny RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Receptors, G-Protein-Coupled / genetics* Receptors, G-Protein-Coupled / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Suppression, Genetic beta Catenin / metabolism
IF 2.74
引用数 12
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
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