title: Evidence of a role of inositol polyphosphate 5-phosphatase INPP5E in cilia formation in zebrafish.
abstract: Inositol phosphatases are important regulators of cell signaling and membrane trafficking. Mutations in inositol polyphosphate 5-phosphatase, INPP5E, have been identified in Joubert syndrome, a rare congenital disorder characterized by midbrain malformation, retinitis pigmentosa, renal cysts, and polydactyly. Previous studies have implicated primary cilia abnormalities in Joubert syndrome, yet the role of INPP5E in cilia formation is not well understood. In this study, we examined the function of INPP5E in cilia development in zebrafish. Using specific antisense morpholino oligonucleotides to knockdown Inpp5e expression, we observed phenotypes of microphthalmia, pronephros cysts, pericardial effusion, and left-right body axis asymmetry. The Inpp5e morphant zebrafish exhibited shortened and decreased cilia formation in the Kupffer's vesicle and pronephric ducts as compared to controls. Epinephrine-stimulated melanosome trafficking was delayed in the Inpp5e zebrafish morphants. Expression of human INPP5E expression rescued the phenotypic defects in the Inpp5e morphants. Taken together, we showed that INPP5E is critical for the cilia development in zebrafish.
authors.affiliation: Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1160 W. Michigan Street, Indianapolis, IN 46202, United States.
authors.forename: Na
authors.initials: N
authors.lastname: Luo
authors.forename: Jingping
authors.initials: J
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002923:Cilia / Q000201:enzymology / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D015151:Immunoblotting; D007150:Immunohistochemistry; D000072181:Inositol Polyphosphate 5-Phosphatases; D020460:Melanosomes / Q000187:drug effects; D023421:Models, Animal; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish
chemical_list: D000316:Adrenergic alpha-Agonists; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D004837:Epinephrine