title: Role of phosphatidylinositol 5-phosphate 4-kinase α in zebrafish development.
abstract: Phosphatidylinositol 5-phosphate 4-kinases (PIP4Ks) phosphorylate phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5-bisphosphate; their most likely function is the regulation of the levels of PI5P, a putative signalling intermediate. There are three mammalian PIP4Ks isoforms (α, β and γ), but their physiological roles remain poorly understood. In the present study, we identified the zebrafish orthologue (zPIP4Kα) of the high-activity human PIP4K α isoform and analyzed its role in embryonic development. RT-PCR analysis and whole-mount in situ hybridization experiments showed that zPIP4Kα is maternally expressed. At later embryonic stages, high PIP4Kα expression was detected in the head and the pectoral fins. Knockdown of zPIP4Kα by antisense morpholino oligonucleotides led to severe morphological abnormalities, including midbody winding defects at 48hpf. The abnormal phenotype could be rescued, at least in large part, by injection of human PIP4Kα mRNA. Our results reveal a key role for PIP4Kα and its activity in vertebrate tissue homeostasis and organ development.
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Dalila
authors.initials: D
authors.lastname: Elouarrat
authors.forename: Yme U
authors.initials: YU
authors.lastname: van der Velden
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Moolenaar
authors.forename: Nullin
authors.initials: N
authors.lastname: Divecha
authors.forename: Anna-Pavlina G
authors.initials: AP
authors.lastname: Haramis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060172:Morpholinos; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D020033:Protein Isoforms; D029961:Zebrafish Proteins; C113567:phosphatidylinositol 5-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C585575:phosphatidylinositol 5-phosphate 4-kinase alpha, zebrafish