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

Abstract

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.