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. Developmental Dynamics 237:3516–3527, 2008. © 2008 Wiley‐Liss, Inc.