Developmental cell-specific regulation of Na(+)-K(+)-ATPase alpha 1-, alpha 2-, and alpha 3-isoform gene expression.
Na(+)-K(+)-activated adenosine triphosphatase (Na(+)-K(+)-ATPase) is the integral membrane protein that maintains the Na(+)-K(+) electrochemical gradient across the plasma membrane. Because of the importance of the Na(+)-K(+) electrochemical gradient to fundamental and specialized cell functions, we investigated the cell-specific modulation of Na(+)-K(+)-ATPase alpha-subunit isoform (alpha 1, alpha 2, and alpha 3) gene expression in different stages of postimplantation mouse embryos and neonatal rat tissues by in situ hybridization with use of isoform-specific rat-derived antisense RNA probes. At early organogenesis (9.5-10.5 days postcoitus), we demonstrated generalized coexpression of alpha 1- and alpha 2-isoforms throughout the mouse embryo with greater levels in the developing but already functional heart, in contrast to the distinct spatially restricted alpha 3-isoform gene expression in the early developing neural tube. At midorganogenesis (15.5-16.5 days postcoitus), differential spatial variation in alpha 1-, alpha 2-, and alpha 3-isoform gene expression was already evident in all organs. Interestingly, region-specific expression patterns within single cell types were noted throughout development and were exemplified by 1) alpha 3-isoform gene expression in marginal cells of the 10.5-day-postcoitus developing neural tube; 2) alpha 1-, alpha 2-, and alpha 3-isoform gene expression in cerebellar granular cells of the 4-day-old rat brain; and 3) alpha 1- and alpha 3-isoform gene expression in 4-day-old rat ventricular cardiomyocytes. These isoform-specific changes in cellular and regional Na(+)-K(+)-ATPase alpha-isoform gene expression may play an active role in development and specialized cell functions.
Herrera
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VL
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University Medical Center, Massachusetts 02118.
Cova
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T
Sassoon
D
D
Ruiz-Opazo
N
N
D000818:Animals; D000831:Animals, Newborn; D016375:Antisense Elements (Genetics); D001755:Blastocyst / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D046911:Macromolecular Substances; D051379:Mice; D009928:Organ Specificity; D011247:Pregnancy; D015347:RNA Probes; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics
D016375:Antisense Elements (Genetics); D007527:Isoenzymes; D046911:Macromolecular Substances; D015347:RNA Probes; D000254:Sodium-Potassium-Exchanging ATPase