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An unconventional myosin, myosin 1d regulates Kupffer's vesicle morphogenesis and laterality

By Manush Saydmohammed, Hisato Yagi, Michael Calderon, Madeline J. Clark, Timothy Feinstein, Ming Sun, Donna B. Stolz, Simon C. Watkins, Jeffrey D. Amack, Cecilia W. Lo, Michael Tsang

Posted 26 Feb 2018
bioRxiv DOI: 10.1101/268789 (published DOI: 10.1038/s41467-018-05866-2)

Establishing left-right (LR) asymmetry is a fundamental process essential for arrangement of visceral organs during development. In vertebrates, motile cilia driven fluid flow in the left-right organizer (LRO) is essential for initiating symmetry breaking event. Without a definite LRO structure in invertebrates, LR asymmetry is initiated at a cellular level by actin-myosin driven chirality. In Drosophila, myosin1D drives tissue-specific chirality in hind-gut looping. Here, we show that myosin 1d (myo1d) is essential for establishing LR asymmetry in zebrafish. Using super-resolution microscopy, we show that the zebrafish LRO, Kupffer's vesicle (KV), fails to form proper lumen size in the absence of myo1d. This process requires directed vacuolar trafficking in KV epithelial cells. Interestingly, the vacuole transporting function of zebrafish Myo1d can be substituted by myosin1C derived from an ancient eukaryote, Acanthamoeba castellanii, where it regulates the transport of contractile vacuoles. Our findings reveal an evolutionarily conserved role for an unconventional myosin in vacuole trafficking, lumen formation and determining laterality.

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