Randomization of Left-Right Asymmetry Due to Loss of Nodal Cilia Generating Leftward Flow of Extraembryonic Fluid in Mice Lacking KIF3B Motor Protein

Cell. 1998 Dec 11;95(6):829-37. doi: 10.1016/s0092-8674(00)81705-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Kif3b protein, mouse
  • Left-Right Determination Factors
  • Transforming Growth Factor beta
  • Kinesin