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Dev Biol October 1, 2010; 346 (1): 39-53.

The ATP-sensitive K(+)-channel (K(ATP)) controls early left-right patterning in Xenopus and chick embryos.

Aw S , Koster JC , Pearson W , Nichols CG , Shi NQ , Carneiro K , Levin M .

Consistent left-right asymmetry requires specific ion currents. We characterize a novel laterality determinant in Xenopus laevis: the ATP-sensitive K(+)-channel (K(ATP)). Expression of specific dominant-negative mutants of the Xenopus Kir6.1 pore subunit of the K(ATP) channel induced randomization of asymmetric organ positioning. Spatio-temporally controlled loss-of-function experiments revealed that the K(ATP) channel functions asymmetrically in LR patterning during very early cleavage stages, and also symmetrically during the early blastula stages, a period when heretofore largely unknown events transmit LR patterning cues. Blocking K(ATP) channel activity randomizes the expression of the left-sided transcription of Nodal. Immunofluorescence analysis revealed that XKir6.1 is localized to basal membranes on the blastocoel roof and cell-cell junctions. A tight junction integrity assay showed that K(ATP) channels are required for proper tight junction function in early Xenopus embryos. We also present evidence that this function may be conserved to the chick, as inhibition of K(ATP) in the primitive streak of chick embryos randomizes the expression of the left-sided gene Sonic hedgehog. We propose a model by which K(ATP) channels control LR patterning via regulation of tight junctions.

PubMed ID: 20643119
PMC ID: PMC2937067
Article link: Dev Biol
Grant support: [+]
Genes referenced: abcc8 kcnj11 kcnj8 mrc1 nodal nodal1 nr4a1 shh tbx2

Article Images: [+] show captions
References [+] :
Adams, Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates. 2006, Pubmed, Xenbase

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