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

作者:Tingler Melanie; Kurz Sabrina; Maerker Markus; Ott Tim; Fuhl Franziska; Schweickert Axel; LeBlanc Straceski Janine M; Noselli Stephane; Blum Martin*
来源:Current Biology, 2018, 28(5): 810-+.
DOI:10.1016/j.cub.2018.01.075

摘要

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.

  • 出版日期2018-3-5