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Curr Biol January 1, 2018; 28 (5): 810-816.e3.

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

Tingler M , Kurz S , Maerker M , Ott T , Fuhl F , Schweickert A , LeBlanc-Straceski JM , Noselli S , Blum M .

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.

PubMed ID: 29478852
Article link: Curr Biol

Species referenced: Xenopus
Genes referenced: actb atf2 dand5 foxj1 foxj1.2 gdf3 lefty myo1d nodal nodal1 pitx2 tekt2 tuba4b vangl2 wnt11b
GO keywords: convergent extension [+]
Antibodies: Fluro-phalloidin Ab2 Tuba4b Ab5
Morpholinos: myo1d MO1

Disease Ontology terms: visceral heterotaxy [+]

Article Images: [+] show captions