title: A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality.
abstract: Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Noël
authors.forename: Manon
authors.initials: M
authors.lastname: Verhoeven
authors.forename: Anne Karine
authors.initials: AK
authors.lastname: Lagendijk
authors.forename: Federico
authors.initials: F
authors.lastname: Tessadori
authors.forename: Kelly
authors.initials: K
authors.lastname: Smith
authors.forename: Suma
authors.initials: S
authors.lastname: Choorapoikayil
authors.forename: Jeroen
authors.initials: J
authors.lastname: den Hertog
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bakkers
mesh_terms: D000199:Actins / Q000502:physiology; D000205:Actomyosin / Q000502:physiology; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D009154:Mutation; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000196:embryology*
chemical_list: D000199:Actins; D055457:Nodal Protein; D000205:Actomyosin