A Conserved Role of the Unconventional Myosin 1d in Laterality Determination

Abstract

Anatomical and functional asymmetries are widespread in the animal kingdom [1, 2]. In vertebrates, many visceral organs are asymmetrically placed [3]. In snails, shells and inner organs coil asymmetrically, and in Drosophila, genitalia and hindgut undergo a chiral rotation during development. The evolutionary origin of these asymmetries remains an open question [1]. Nodal signaling is widely used [4], and many, but not all, vertebrates use cilia for symmetry breaking [5]. In Drosophila, which lacks both cilia and Nodal, the unconventional myosin ID (myo1d) gene controls dextral rotation of chiral organs [6, 7]. Here, we studied the role of myo1d in left-right (LR) axis formation in Xenopus. Morpholino oligomer-mediated myo1d downregulation affected organ placement in >50% of morphant tadpoles. Induction of the left-asymmetric Nodal cascade was aberrant in >70% of cases. Expression of the flow-target gene dand5 was compromised, as was flow itself, due to shorter, fewer, and non-polarized cilia at the LR organizer. Additional phenotypes pinpointed Wnt/planar cell polarity signaling and suggested that myo1d, like in Drosophila [8], acted in the context of the planar cell polarity pathway. Indeed, convergent extension of gastrula explant cultures was inhibited in myo1d morphants, and the ATF2 reporter gene for non-canonical Wnt signaling was downregulated. Finally, genetic interference experiments demonstrated a functional interaction between the core planar cell polarity signaling gene vangl2 and myo1d in LR axis formation. Thus, our data identified myo1d as a common denominator of arthropod and chordate asymmetry, in agreement with a monophyletic origin of animal asymmetry.

The development of CRISPR for a mollusc establishes the formin Lsdia1 as the long-sought gene for snail dextral/sinistral coiling

“…Left-right body asymmetry is established by tightly regulated genetic processes. Interest has centred on the diverse mechanisms proposed for different phyla, the possibility of a unified mechanism (Blum et al, 2014;Coutelis et al, 2014;Juan et al, 2018;Nakamura and Hamada, 2012;Tingler et al, 2018;Vandenberg and Levin, 2013) and the involvement of cellular chirality (Danilchik et al, 2006;González-Morales et al, 2015;Meshcheryakov and Beloussov, 1975;Schonegg et al, 2014;Taniguchi et al, 2011;Tee et al, 2016;Wan et al, 2011); however, many important aspects are unresolved. To study the molecular and cellular mechanisms of chiromorphogenesis, we have used the snail Lymnaea (L.) stagnalis as an organism with unique advantages.…”

The Drosophila actin nucleator DAAM is essential for left-right asymmetry

“…Hence, while Drosophila rely exclusively on actin-based processes, vertebrates use both systems (actin and microtubules) for establishing LR asymmetry. Nevertheless, Myo1D is the sole common denominator between invertebrates and vertebrates [14,15], and it will be interesting to characterize how Myo1D, actin and microtubules interact for establishing vertebrate LR asymmetry.…”

“…be interesting to know if, in addition to Xenopus and zebrafish [14,15], Myo1D plays any role in chick LR asymmetry. Our recent work showed a link between Myo1D and Planar Cell Polarity (PCP) in Drosophila, zebrafish and Xenopus [9,15,36], and Daam1 function has been shown to be involved in PCP-mediated renal tubulogenesis [37], suggesting a conserved Myo1D-DAAM-PCP link. In the pond snail Lymnaea stagnalis, some natural variants show a sinistral phenotype in their shell coiling.…”

“…Interestingly, recent work showed that myo1D is also involved in LR asymmetry of Xenopus and zebrafish [14,15], hence myo1D represents a unique dextral determinant whose function is conserved across phyla. These findings, together with the existence of nodal-independent mechanisms for LR development of the heart [16], further suggest that myo1D-dependent and actin-based processes may represent a unifying mechanism controlling LR asymmetry in both vertebrates and invertebrates.…”

Making and breaking symmetry in development, growth and disease

“…There is evidence that actomyosin components, such as Myo1D, control L-R asymmetry in many deuterostomes as well as the model ecdysozoans Drosophila and C. elegans, supporting an ancestral role for the cytoskeleton in generating L-R asymmetry within the bilateria (Lebreton et al, 2018;Yuan and Brueckner, 2018). Disruption of Myo1D in the model vertebrates Xenopus laevis and zebrafish results in L-R defects owing to perturbation of left-right organizer flow (Juan et al, 2018;Saydmohammed et al, 2018;Tingler et al, 2018).…”