title: Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.
abstract: Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning. lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wild-type nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.
authors.affiliation: Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nonaka
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: A
authors.initials: A
authors.lastname: Harada
authors.forename: Y
authors.initials: Y
authors.lastname: Kanai
authors.forename: M
authors.initials: M
authors.lastname: Kido
authors.forename: N
authors.initials: N
authors.lastname: Hirokawa
mesh_terms: D000818:Animals; D002923:Cilia; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D016547:Kinesins / Q000235:genetics / Q000502:physiology*; D055458:Left-Right Determination Factors; D051379:Mice; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: C490672:Kif3b protein, mouse; D055458:Left-Right Determination Factors; D016212:Transforming Growth Factor beta; D016547:Kinesins