Cystic kidney gene seahorse regulates cilia-mediated processes and Wnt pathways.
Recently the cilium has emerged as an important sensory organelle for a wide range of cell types in vertebrates. However, the signaling cascade that links ciliary signals to cellular events remains poorly understood. Here, we show that the zebrafish cystic kidney gene seahorse is closely associated with ciliary functions: seahorse is required for establishing left-right asymmetry and for preventing kidney cyst formation; seahorse transcript is highly enriched in heavily ciliated tissues; and seahorse genetically interacts with the ciliary gene inversin. Yet seahorse is dispensable for cilia assembly or motility and the Seahorse protein is cytoplasmic. We provide evidence that Seahorse associates with Dishevelled. Finally, we show that seahorse constrains the canonical Wnt pathway and promotes the noncanonical Wnt pathway during gastrulation. Together, these data suggest that Seahorse may provide a link between ciliary signals and Wnt pathways.
Kishimoto
Norihito
N
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, NSB-393, New Haven, CT 06520, USA.
Cao
Ying
Y
Park
Alice
A
Sun
Zhaoxia
Z
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian; D005775:Gastrula; D017403:In Situ Hybridization; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018715:Microscopy, Video; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C529964:Lrrc6 protein, zebrafish; D010750:Phosphoproteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins