The nodal inhibitor Coco is a critical target of leftward flow in Xenopus

Curr Biol. 2010 Apr 27;20(8):738-43. doi: 10.1016/j.cub.2010.02.061. Epub 2010 Apr 8.


Vertebrate laterality, which is manifested by asymmetrically placed organs [1], depends on asymmetric activation of the Nodal signaling cascade in the left lateral plate mesoderm [2]. In fish, amphibians, and mammals, a cilia-driven leftward flow of extracellular fluid acts upstream of the Nodal cascade [3-6]. The direct target of flow has remained elusive. In Xenopus, flow occurs at the gastrocoel roof plate (GRP) in the dorsal midline of the embryo [4, 7]. The GRP is bordered by a second, bilaterally symmetrical Nodal expression domain [8]. Here we identify the Nodal inhibitor Coco as a critical target of flow. Coco and Xenopus Nodal-related 1 (Xnr1) are coexpressed in the lateralmost ciliated GRP cells. Coco becomes downregulated on the left side of the GRP as a direct readout of flow. Ablation of flow prevented Coco repression, whereas Xnr1 expression was independent of flow. Loss of flow-induced laterality defects were rescued by knockdown of Coco on the left side. Parallel knockdown of Coco and Xnr1 in GRP cells restored laterality defects in flow-impaired embryos, demonstrating that Coco acted through GRP-expressed Xnr1. Coco thus acts as a critical target of flow, suggesting that symmetry is broken by flow-mediated left-asymmetric release of Nodal repression at the midline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / physiology
  • Embryonic Induction
  • Morphogenesis / physiology*
  • Nodal Protein / antagonists & inhibitors*
  • Nodal Protein / metabolism
  • Signal Transduction / physiology
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / anatomy & histology*
  • Xenopus laevis / embryology*


  • DAND5 protein, Xenopus
  • Nodal Protein
  • Xenopus Proteins
  • nodal1 protein, Xenopus