title: Sodium pump activity in the yolk syncytial layer regulates zebrafish heart tube morphogenesis.
abstract: Na(+),K(+) ATPase pumps Na(+) out of and K(+) into the cytosol, maintaining a resting potential that is essential for the function of excitable tissues like cardiac muscle. In addition to its well-characterized physiological role in the heart, Na(+),K(+) ATPase also regulates the morphogenesis of the embryonic zebrafish heart via an as yet unknown mechanism. Here, we describe a novel non-cell autonomous function of Na(+),K(+) ATPase/Atp1a1 in the elongation of the zebrafish heart tube. Embryos lacking Atp1a1 function exhibit abnormal migration behavior of cardiac precursors, defects in the elongation of the heart tube, and a severe reduction in ECM/Fibronectin deposition around the myocardium, despite the presence of normal cell polarity and junctions in the myocardial epithelium prior to the timeframe of heart tube elongation. Interestingly, we found that Atp1a1 is not present in the myocardium at the time when cardiac morphogenesis defects first become apparent, but is expressed in an extra-embryonic tissue, the yolk syncytial layer (YSL), at earlier stages. Knockdown of Atp1a1 activity specifically in the YSL using morpholino oligonucleotides produced heart tube elongation defects like those found in atp1a1 mutants, indicating that Atp1a1 function in the YSL is necessary for heart tube elongation. Furthermore, atp1a1 expression in the YSL was regulated by the homeobox transcription factor mxtx1. Together, these data reveal a new non-cell autonomous role for Atp1a1 in cardiac morphogenesis and establish Na(+),K(+) ATPase as a major player in the genetic pathway by which the YSL regulates embryonic ECM deposition.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Langenbacher
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Jau-Nian
authors.initials: JN
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004527:Egg Proteins / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000502:physiology*; D060172:Morpholinos / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D004527:Egg Proteins; D018398:Homeodomain Proteins; D060172:Morpholinos; D029961:Zebrafish Proteins; C409449:mxtx1 protein, zebrafish; C439245:atp1a1a.1 protein, zebrafish; D000254:Sodium-Potassium-Exchanging ATPase