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Updated: May 6, 2026

A Micropatterning Assay for Measuring Cell Chirality
Published on: March 11, 2022
A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality
Emily S Noël1, Manon Verhoeven, Anne Karine Lagendijk
1Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
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.
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