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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.

Pubmed ID: 9865700

Authors

  • Nonaka S
  • Tanaka Y
  • Okada Y
  • Takeda S
  • Harada A
  • Kanai Y
  • Kido M
  • Hirokawa N

Journal

Cell

Publication Data

December 11, 1998

Associated Grants

None

Mesh Terms

  • Animals
  • Cilia
  • Embryonic and Fetal Development
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Kinesin
  • Left-Right Determination Factors
  • Mice
  • Transforming Growth Factor beta