Gap junctions relay FGF8-mediated right-sided repression of Nodal in rabbit

Dev Dyn. 2008 Dec;237(12):3516-27. doi: 10.1002/dvdy.21535.

Abstract

In vertebrate gastrula/neurula embryos, a cilia-driven leftward flow asymmetrically activates the Nodal cascade in the left lateral plate mesoderm (LPM). In frog embryos left-right axis formation was postulated to depend on gap junctions (GJs) during cleavage. Here, we show that GJs cooperate with fibroblast growth factor-8 (FGF8) to specify asymmetric Nodal in the rabbit embryo at gastrula/neurula. GJs and FGF signaling were manipulated in whole embryo and explant cultures of rabbit blastodiscs. These experiments demonstrate that right-sided inhibition of Nodal by FGF8 depended on intercellular communication by means of GJs, and that left-sided induction of Nodal required attenuation of gap junctional communication (GJC). Before flow, the left and right side were equally competent but actively prevented from Nodal induction through FGF8/GJ. Our data suggest that flow unilaterally attenuates FGF8/GJ-mediated repression of Nodal on the left side, integrating GJC and FGF8 into the flow-based mechanism of symmetry breakage in the vertebrate embryo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Connexin 43 / metabolism
  • Embryo, Mammalian / drug effects
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Fibroblast Growth Factor 8 / antagonists & inhibitors
  • Fibroblast Growth Factor 8 / genetics
  • Fibroblast Growth Factor 8 / metabolism*
  • Gap Junctions / metabolism*
  • Gene Expression Regulation, Developmental
  • Heptanol / pharmacology
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Nodal Protein / metabolism*
  • Rabbits

Substances

  • Connexin 43
  • Nodal Protein
  • Fibroblast Growth Factor 8
  • Heptanol