Current Biology
Volume 28, Issue 5, 5 March 2018, Pages 810-816.e3
Journal home page for Current Biology

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

https://doi.org/10.1016/j.cub.2018.01.075Get rights and content
Under an Elsevier user license
open archive

Highlights

  • The unconventional myosin 1D is required for vertebrate left-right asymmetry

  • Loss of myo1d causes aberrant leftward flow and laterality defects in Xenopus

  • The function of myosin1D is mediated through the planar cell polarity pathway

  • Myosin 1D links laterality in arthropods and chordates

Summary

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.

Keywords

myold
left-right asymmetry
cilia
planar cell polarity
PCP
Xenopus
left-right organizer
gastroeol roof plate
myosin

Cited by (0)

4

These authors contributed equally

5

Lead Contact