Asymmetries in H+/K+-ATPase and Cell Membrane Potentials Comprise a Very Early Step in Left-Right Patterning

Cell. 2002 Oct 4;111(1):77-89. doi: 10.1016/s0092-8674(02)00939-x.

Abstract

A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Animals
  • Barium Compounds / pharmacology
  • Body Patterning*
  • Cell Membrane / metabolism*
  • Chick Embryo
  • Chlorides / pharmacology
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • H(+)-K(+)-Exchanging ATPase / chemistry*
  • H(+)-K(+)-Exchanging ATPase / metabolism*
  • In Situ Hybridization
  • Lansoprazole
  • Membrane Potentials*
  • Molecular Sequence Data
  • Omeprazole / analogs & derivatives*
  • Omeprazole / pharmacology
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Proton Pump Inhibitors
  • RNA, Messenger / metabolism
  • Time Factors
  • Xenopus

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Barium Compounds
  • Chlorides
  • Enzyme Inhibitors
  • Potassium Channels, Inwardly Rectifying
  • Proton Pump Inhibitors
  • RNA, Messenger
  • Lansoprazole
  • barium chloride
  • H(+)-K(+)-Exchanging ATPase
  • Omeprazole

Associated data

  • GENBANK/AL588035