Myosin1D is an evolutionarily conserved regulator of animal Left/Right asymmetry

Thomas Juan, Charles Géminard, Jean-Baptiste Coutelis, Delphine Cerezo, Sophie Polès, Stéphane Noselli, and Maximilian Fürthauer

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Received: 5th February 18

The establishment of Left/Right (LR) asymmetry is fundamental to animal development. While the pathways governing antero-posterior and dorso-ventral patterning are well conserved among different phyla, divergent mechanisms have been implicated in the specification of LR asymmetry in vertebrates and invertebrates. A cilia-driven, directional fluid flow is important for symmetry breaking in numerous vertebrates, including zebrafish1-10. Alternatively, LR asymmetry can be established independently of motile cilia, notably through the intrinsic chirality of the acto-myosin cytoskeleton11-18. Here we show that Myosin1D (Myo1D), which has been previously identified as a key regulator of LR asymmetry in Drosophila12,13, is essential for the formation and the function of the zebrafish LR Organizer (LRO). We show that Myo1D controls the polarity of LRO cilia and interacts functionally with the Planar Cell Polarity (PCP) gene VanGogh-like2 (Vangl2)19 to promote the establishment of a functional LRO flow. Our findings identify Myo1D as the first evolutionarily conserved regulator of animal LR asymmetry, and show that functional interactions between Myo1D and PCP are central to the establishment of animal LR asymmetry.

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