title: Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II.
abstract: The embryonic cellular events that set the asymmetry of the genetic control circuit controlling left-right (L-R) axis determination in mammals are poorly understood. New insight into this problem was obtained by analyzing mouse mutants lacking the KIF3A motor subunit of the kinesin-II motor complex. Embryos lacking KIF3A die at 10 days postcoitum, exhibit randomized establishment of L-R asymmetry, and display numerous structural abnormalities. The earliest detectable abnormality in KIF3A mutant embryos is found at day 7.5, where scanning electron microscopy reveals loss of cilia ordinarily present 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 phenotype 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 morphogenesis is conserved from Chlamydomonas to mammals and support the view that embryonic cilia play a role in the earliest cellular determinative events establishing L-R asymmetry.
authors.affiliation: Division of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Marszalek
authors.forename: P
authors.initials: P
authors.lastname: Ruiz-Lozano
authors.forename: E
authors.initials: E
authors.lastname: Roberts
authors.forename: K R
authors.initials: KR
authors.lastname: Chien
authors.forename: L S
authors.initials: LS
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002923:Cilia / Q000235:genetics* / Q000648:ultrastructure; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016547:Kinesins; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009024:Morphogenesis / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D011247:Pregnancy
chemical_list: D002135:Calcium-Binding Proteins; D009124:Muscle Proteins; C074152:kinesin-II; D016547:Kinesins