Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.
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.
Nonaka
S
S
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Japan.
Tanaka
Y
Y
Okada
Y
Y
Takeda
S
S
Harada
A
A
Kanai
Y
Y
Kido
M
M
Hirokawa
N
N
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
C490672:Kif3b protein, mouse; D055458:Left-Right Determination Factors; D016212:Transforming Growth Factor beta; D016547:Kinesins