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