Nodal asymmetry and hedgehog signaling during vertebrate left–right symmetry breaking

Development of visceral left–right asymmetry in bilateria is based on initial symmetry breaking followed by subsequent asymmetric molecular patterning. An important step is the left-sided expression of transcription factor
pitx2
which is mediated by asymmetric expression of the
nodal
morphogen in the left lateral plate mesoderm of vertebrates. Processes leading to emergence of the asymmetric
nodal
domain differ depending on the mode of symmetry breaking. In
Xenopus laevis
and mouse embryos, the leftward fluid flow on the ventral surface of the left–right organizer leads through intermediate steps to enhanced activity of the nodal protein on the left side of the organizer and subsequent asymmetric
nodal
induction in the lateral plate mesoderm. In the chick embryo, asymmetric morphogenesis of axial organs leads to paraxial
nodal
asymmetry during the late gastrulation stage. Although it was shown that hedgehog signaling is required for initiation of the
nodal
expression, the mechanism of its asymmetry remains to be clarified. In this study, we established the activation of hedgehog signaling in early chick embryos to further study its role in the initiation of asymmetric
nodal
expression. Our data reveal that hedgehog signaling is sufficient to induce the
nodal
expression in competent domains of the chick embryo, while treatment of
Xenopus
embryos led to moderate
nodal
inhibition. We discuss the role of symmetry breaking and competence in the initiation of asymmetric gene expression.