Structural and Functional Characterization of the FGF Signaling Pathway in Regeneration of the Polychaete Worm Alitta virens (Annelida, Errantia)

Genes (Basel). 2021 May 21;12(6):788. doi: 10.3390/genes12060788.


Epimorphic regeneration of lost body segments is a widespread phenomenon across annelids. However, the molecular inducers of the cell sources for this reparative morphogenesis have not been identified. In this study, we focused on the role of fibroblast growth factor (FGF) signaling in the posterior regeneration of Alitta virens. For the first time, we showed an early activation of FGF ligands and receptor expression in an annelid regenerating after amputation. The expression patterns indicate that the entire regenerative bud is competent to FGFs, whose activity precedes the initiation of cell proliferation. The critical requirement of FGF signaling, especially at early stages, is also supported by inhibitor treatments followed by proliferation assay, demonstrating that induction of blastemal cells depends on FGFs. Our results show that FGF signaling pathway is a key player in regenerative response, while the FGF-positive wound epithelium, ventral nerve cord and some mesodermal cells around the gut could be the inducing tissues. This mechanism resembles reparative regeneration of vertebrate appendages suggesting such a response to the injury may be ancestral for all bilaterians.

Keywords: Nereis; SU5402; annelids; axis elongation; blastema induction; dedifferentiation; evolution; fibroblast growth factor; invertebrates; segmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annelida / genetics
  • Annelida / metabolism*
  • Annelida / physiology
  • Cell Proliferation
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism
  • Regeneration*
  • Signal Transduction


  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors