4.7 Article

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

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.957211

Keywords

left-right (LR) asymmetry; chick embryo; nodal; hedgehog signaling; heart looping; Xenopus laevis embryo; embryonic competence

Funding

  1. Koltzov Institute of Developmental Biology
  2. [0088-2021-0009]

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The development of visceral left-right asymmetry in bilateria relies on initial symmetry breaking and subsequent molecular patterning. The expression of the transcription factor pitx2 on the left side is facilitated by the asymmetric expression of the nodal morphogen in the left lateral plate mesoderm. The mechanisms leading to the asymmetric nodal domain differ depending on the mode of 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.

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