Wnt11b is involved in cilia-mediated symmetry breakage during Xenopus left-right development

PLoS One. 2013 Sep 13;8(9):e73646. doi: 10.1371/journal.pone.0073646. eCollection 2013.

Abstract

Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP) give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1, a regulator of motile cilia, and Wnt/planar cell polarity (PCP) dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM), from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Cell Movement
  • Cell Polarity
  • Cilia / genetics
  • Cilia / metabolism*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gastrula / embryology
  • Gastrula / metabolism*
  • Gene Expression Regulation, Developmental*
  • Mesoderm / cytology
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Neurulation / genetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • Xenopus Proteins / genetics*
  • Xenopus Proteins / metabolism
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics*
  • Xenopus laevis / metabolism

Substances

  • DAND5 protein, Xenopus
  • FOXJ1 protein, Xenopus
  • Forkhead Transcription Factors
  • Protein Isoforms
  • Wnt Proteins
  • Xenopus Proteins
  • nodal1 protein, Xenopus
  • wnt11b protein, Xenopus

Grant support

This work was supported by DFG Grant BL285/9-1 to MB. PW was recipient of a PhD fellowship from the Landesgraduiertenförderung Baden-Württemberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.