XB-ART-55915Development May 10, 2019; 146 (9):
Organ left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). While the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development are conserved, diverging results from different model organisms suggested a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel to FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca2+-branch is required for specification of the flow sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification, namely for generating and sensing of leftward flow. Moreover, our findings in Xenopus demonstrate that FGF functions in LR development share more conserved features across vertebrate species than previously anticipated.
PubMed ID: 31036544
Article link: Development
Genes referenced: a2ml1 dand5 dnah9 fgf8 fgfr1 foxj1 myf5 myod1 nodal nodal3.1 pkd2 shh spry1 tbxt tekt2
GO keywords: nodal signaling pathway involved in determination of left/right asymmetry