title: Cilia-driven leftward flow determines laterality in Xenopus.
abstract: Determination of the vertebrate left-right body axis during embryogenesis results in asymmetric development and placement of most inner organs. Although the asymmetric Nodal cascade is conserved in all vertebrates, the mechanism of symmetry breakage has remained controversial. In mammalian and fish embryos, a cilia-driven leftward flow of extracellular fluid is required for initiation of the Nodal cascade. This flow is localized at the posterior notochord ("node") and Kupffer's vesicle, respectively. In frog and chick embryos, however, molecular asymmetries are required earlier, from cleavage stages through gastrulation. The validity of a cilia-based mechanism for all vertebrates therefore has been questioned. Here we show that a cilia-driven leftward flow precedes asymmetric nodal expression in the frog Xenopus. Motile monocilia emerged on the gastrocoel roof plate during neurulation and lengthened and polarized from an initially central position to the posterior pole of cells. Concomitantly, a robust leftward fluid flow developed from stage 15 onward, significantly before asymmetric nodal transcription started in the left-lateral-plate mesoderm at stage 19. Injection of 1.5% methylcellulose into the archenteron prevented leftward flow and resulted in laterality defects, demonstrating that the flow itself was required for asymmetric gene expression and organ placement.
authors.affiliation: University of Hohenheim, Institute of Zoology, D-70593 Stuttgart, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schweickert
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.forename: Tina
authors.initials: T
authors.lastname: Beyer
authors.forename: Philipp
authors.initials: P
authors.lastname: Vick
authors.forename: Susanne
authors.initials: S
authors.lastname: Bogusch
authors.forename: Kerstin
authors.initials: K
authors.lastname: Feistel
authors.forename: Martin
authors.initials: M
authors.lastname: Blum
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D005775:Gastrula / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D012212:Rheology; D014981:Xenopus / Q000196:embryology*