title: Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry.
abstract: Signaling by Nodal and Bmp is essential for cardiac laterality. How activities of these pathways translate into left-right asymmetric organ morphogenesis is largely unknown. We show that, in zebrafish, Nodal locally reduces Bmp activity on the left side of the cardiac field. This effect is mediated by the extracellular matrix enzyme Hyaluronan synthase 2, expression of which is induced by Nodal. Unilateral reduction of Bmp signaling results in lower expression of nonmuscle myosin II and higher cell motility on the left, driving asymmetric displacement of the entire cardiac field. In silico modeling shows that left-right differences in cell motility are sufficient to induce a robust, directional migration of cardiac tissue. Thus, the mechanism underlying the formation of cardiac left-right asymmetry involves Nodal modulating an antimotogenic Bmp activity.
authors.affiliation: Cardiovascular Department, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors.forename: Justus
authors.initials: J
authors.lastname: Veerkamp
authors.forename: Franziska
authors.initials: F
authors.lastname: Rudolph
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Cseresnyes
authors.forename: Florian
authors.initials: F
authors.lastname: Priller
authors.forename: Cécile
authors.initials: C
authors.lastname: Otten
authors.forename: Marc
authors.initials: M
authors.lastname: Renz
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
authors.forename: Salim
authors.initials: S
authors.lastname: Abdelilah-Seyfried
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D018507:Gene Expression Regulation, Developmental; D014453:Glucuronosyltransferase / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D000076002:Hyaluronan Synthases; D055458:Left-Right Determination Factors; D055457:Nodal Protein / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D029961:Zebrafish Proteins; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; C491095:has2 protein, zebrafish; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB