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XB-ART-45700
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.



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.

PubMed ID: 22832275
Article link: Cell Rep

Genes referenced: atp4a pitx2 en2 twist1 atp1b1 sox3 foxj1 actl6a cat.2 ctnnb1 foxj1.2 gnl3 inhba rho rho.2 tbx2
Antibodies: Atp4a
Morpholinos: atp4a MO1


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