Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II

The embryonic cellular events that set the asymmetry of the genetic control circuit controlling left-right (L-R) axis determination in mammals are poo rly understood. New insight into this problem was obtained by analyzing mou se mutants lacking the KIF3A motor subunit of the kinesin-II motor complex. Embryos lacking KIF3A die at 10 days postcoitum, exhibit randomized establ ishment of L-R asymmetry, and display numerous structural abnormalities. Th e earliest detectable abnormality in KIF3A mutant embryos is found at day 7 .5, where scanning electron microscopy reveals loss of cilia ordinarily pre sent on cells of the wild-type embryonic node, which is thought to play an important role in setting the initial L-R asymmetry. This cellular phenotyp e is observed before the earliest reported time of asymmetric expression of markers of the L-R signaling pathway. These observations demonstrate that the kinesin-based transport pathway needed for flagellar and ciliary morpho genesis is conserved from Chlamydomonas to mammals and support the view tha t embryonic cilia play a role in the earliest cellular determinative events establishing L-R asymmetry.