Gap junctions relay FGF8-mediated right-sided repression of Nodal in rabbit.
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.
University of Hohenheim, Institute of Zoology, Stuttgart, Germany.
Kerstin
K
Feistel
Martin
M
Blum
D000818:Animals; D019521:Body Patterning; D018031:Connexin 43 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D019850:Heptanol / Q000494:pharmacology; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D055457:Nodal Protein / Q000378:metabolism*; D011817:Rabbits
D018031:Connexin 43; D055457:Nodal Protein; D051524:Fibroblast Growth Factor 8; D019850:Heptanol