The Nodal Inhibitor Coco Is a Critical Target of Leftward Flow in Xenopus.

Publikations-Art

Zeitschriftenbeitrag

Autoren

Schweickert A, Vick P, Getwan M, Weber T, Schneider I, Eberhardt M, Beyer T, Pachur A, Blum M.

Erscheinungsjahr

2010

Veröffentlicht in

Current Biology

Vertebrate laterality, which is manifested by asymmetrically placed organs, depends on asymmetric activation of the Nodal signaling cascade in the left lateral plate mesoderm. In fish, amphibians, and mammals, a cilia-driven leftward flow of extracellular fluid acts upstream of the Nodal cascade. 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. The GRP is bordered by a second, bilaterally symmetrical Nodal expression domain. 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.