Myosin1D regulates animal left-right asymmetry

The characterization of a unifying mechanism governing left-right asymmetry in different phyla has long remained elusive. We show that Myosin1D, a previously identified regulator of Drosophila left-right asymmetry, is essential for the formation and function of the zebrafish left-right organizer, identifying thereby an evolutionarily conserved regulator of animal laterality.

HFSP Career Development Award holder Maximilian F├╝rthauer and colleagues
authored on Thu, 19 July 2018

The molecular pathways governing anteroposterior and dorsoventral patterning have been extensively conserved throughout evolution. In contrast, the mechanisms that control LR asymmetry have been found to be seemingly very diverse across, but also within, different phyla. Processes that have been implicated in symmetry breaking range from cilia-driven fluid flows and localized ion flows to cellular rearrangements dependent on cytoskeletal polarity. This apparent diversity raises the question whether a unifying mechanism underlying the establishment of LR asymmetry in different animal species remains yet to be identified.

An attractive hypothesis is that the chirality of actin filaments may provide a template for LR asymmetry. Actin-binding proteins govern molecular and cellular chirality and actin-dependent processes regulate invertebrate and vertebrate laterality. Studies in Drosophila have identified the actin-based molecular motor Myosin1D (Myo1D) as a determinant of LR asymmetry. Our work shows that Myosin1D is essential for the formation and function of the zebrafish LR Organizer (LRO). The zebrafish LRO is an epithelial vesicle that is decorated on its inside by motile mono-cilia, the beating of which creates a directional, symmetry-breaking fluid flow. Our work shows that Myo1D controls zebrafish left-right asymmetry by exerting an essential control on LRO motile cilia orientation.

Figure. Myosin1D is an evolutionarily conserved regulator of animal left-right asymmetry.
In the zebrafish as well as in several other vertebrate species, motile cilia promote the formation of a directional, symmetry-breaking fluid flow. In contrast, cilia are not involved in the establishment of left-right asymmetry in Drosophila, which depends on proteins that interact with the Actin cytoskeleton. Despite these seemingly different mechanisms, the Actin-binding motor protein Myosin1D is required for the establishment of left-right asymmetry in both fish and flies, revealing a fundamentally conserved mechanism underlying the establishment of animal laterality.

During the asymmetric morphogenesis of the Drosophila hindgut, Myo1D interacts with different components of the Planar Cell Polarity (PCP) pathway to promote chiral tissue torsion. We show that in the zebrafish, Myo1D interacts functionally with the PCP gene VanGogh-like2 (Vangl2) to control cilia orientation and shape a productive LRO flow. Our findings identify Myo1D as an evolutionarily conserved determinant of LR asymmetry, and show that functional interactions between Myo1D and PCP are central to the establishment of animal LR asymmetry. The support of an HFSP Career Development Award was crucial to the realization of this research work, as it provided us with the freedom to embark in a collaborative research project and explore an entirely new research avenue.

Reference

Myosin1D is an evolutionarily conserved regulator of animal left-right asymmetry. Juan T, Géminard C, Coutelis JB, Cerezo D, Polès S, Noselli S, Fürthauer M. Nat Commun. 2018 May 16;9(1):1942. doi: 10.1038/s41467-018-04284-8.

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