FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step EMT

Abstract

Mesoderm induction begins during gastrulation. Recent evidence from several vertebrate species indicates mesoderm induction continues after gastrulation in neuromesodermal progenitor cells (NMPs) within the posterior-most embryonic structure called the tailbud. It is unclear to what extent the molecular mechanisms of mesoderm induction are conserved between gastrula and post-gastrula stages of development. Fibroblast growth factor (FGF) signaling is required for mesoderm induction during gastrulation through positive transcriptional regulation of the t-box transcription factor brachyury (ntla in zebrafish). We find that FGF is continuously required for paraxial mesoderm (PM) induction in post-gastrula NMPs, but has the opposite effect on brachyury expression. FGF signaling represses brachyury and the NMP marker sox2 through regulation of tbx16 and msgn1, thereby committing cells to a PM fate. FGF mediated PM induction in NMPs functions in tight coordination with canonical Wnt signaling during the epithelial to mesenchymal transition from NMP to mesodermal progenitor. Wnt signaling initiates the EMT, while FGF signaling terminates this event. Our results indicate that germ layer induction in the tailbud is not a simple continuation of gastrulation events.