title: ATP4a is required for Wnt-dependent Foxj1 expression and leftward flow in Xenopus left-right development.
abstract: Most vertebrate embryos break symmetry by a cilia-driven leftward flow during neurulation. In the frog Xenopus asymmetric expression of the ion pump ATP4a was reported at the 4-cell stage. The "ion-flux" model postulates that symmetry is broken flow-independently through an ATP4-generated asymmetric voltage gradient that drives serotonin through gap junctions to one side of the embryo. Here, we show that ATP4a is symmetrically expressed. Gene knockdown or pharmacological inhibition compromised organ situs, asymmetric marker gene expression, and leftward flow. The gastrocoel roof plate (GRP), where flow in frog occurs, revealed fewer, shortened, and misaligned cilia. Foxj1, a master control gene of motile cilia, was downregulated in the superficial mesoderm, from which the GRP develops. Specifically, ATP4 was required for Wnt/β-catenin-regulated Foxj1 induction and Wnt/PCP-dependent cilia polarization. Our work argues for evolutionary conservation of symmetry breakage in the vertebrates.
authors: University of Hohenheim, Institute of Zoology, Garbenstrasse 30, 70593 Stuttgart, Germany.
authors: Peter
authors: P
authors: Walentek
authors: Tina
authors: T
authors: Beyer
authors: Thomas
authors: T
authors: Thumberger
authors: Axel
authors: A
authors: Schweickert
authors: Martin
authors: M
authors: Blum
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002923:Cilia / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000502:physiology; D016623:Ion Pumps / Q000235:genetics / Q000502:physiology*; D054261:Neurulation / Q000235:genetics / Q000502:physiology; D017494:Proton Pumps / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C490956:FOXJ1 protein, Xenopus; D051858:Forkhead Transcription Factors; D016623:Ion Pumps; D017494:Proton Pumps; D051153:Wnt Proteins; D029867:Xenopus Proteins; C579782:ATP4a protein, Xenopus; D017506:H(+)-K(+)-Exchanging ATPase