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.