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Cell Rep May 31, 2012; 1 (5): 516-27.

ATP4a is required for Wnt-dependent Foxj1 expression and leftward flow in Xenopus left-right development.

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.

PubMed ID: 22832275
Article link: Cell Rep

Species referenced: Xenopus
Genes referenced: actl6a atp1b1 atp4a cat.2 ctnnb1 en2 foxj1 foxj1.2 gnl3 inhba pitx2 rho rho.2 sox3 tbx2 twist1
Morpholinos: atp4a MO1

Phenotypes: Xla Wt + SCH28080 (fig.1.f) [+]

Article Images: [+] show captions