A mutation in the zebrafish Na,K-ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left-right asymmetry downstream or in parallel to nodal flow.
While there is a good conceptual framework of dorsoventral and anterioposterior axes formation in most vertebrate groups, understanding of left-right axis initiation is fragmentary. Diverse mechanisms have been implied to contribute to the earliest steps of left-right asymmetry, including small molecule signals, gap junctional communication, membrane potential, and directional flow of extracellular liquid generated by monocilia in the node region. Here we demonstrate that a mutation in the zebrafish Na,K-ATPase subunit atp1a1a causes left-right defects including isomerism of internal organs at the anatomical level. The normally left-sided Nodal signal spaw as well as its inhibitor lefty are expressed bilaterally, while pitx2 may appear random or bilateral. Monocilia movement and fluid circulation in Kupffer's vesicle are normal in atp1a1a(m883) mutant embryos. Therefore, the Na,K-ATPase is required downstream or in parallel to monocilia function during initiation of left-right asymmetry in zebrafish.
Ellertsdottir
Elin
E
Developmental Biology, Institute Biology 1, University of Freiburg, Freiburg, Germany.
Ganz
Julia
J
Dürr
Katrin
K
Loges
Niki
N
Biemar
Frederic
F
Seifert
Franziska
F
Ettl
Anne-Katrin
AK
Kramer-Zucker
Albrecht K
AK
Nitschke
Roland
R
Driever
Wolfgang
W
D000818:Animals; D001692:Biological Transport; D019521:Body Patterning; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D021122:Protein Subunits; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D008565:Membrane Proteins; D021122:Protein Subunits; D029961:Zebrafish Proteins; C501108:nomo protein, zebrafish; C439245:atp1a1a.1 protein, zebrafish; D000254:Sodium-Potassium-Exchanging ATPase