Abstract
ABSTRACTRegeneration as an adult developmental process is in many aspects similar to embryonic development. Although many studies point out similarities and differences, no large-scale, direct and functional comparative analyses between development and regeneration of a specific cell type or structure in one animal exist. Here, we use the brittle star Amphiura filiformis to characterise the role of the FGF signalling pathway during skeletal development in embryos and arm regeneration. In both processes, we find ligands expressed in ectodermal cells that flank underlying skeletal mesenchymal cells, which express the receptors. Perturbation of FGF signalling showed inhibited skeleton formation in both embryogenesis and regeneration, without affecting other key developmental processes. Differential transcriptome analysis finds mostly differentiation genes rather than transcription factors to be downregulated in both contexts. Moreover, comparative gene analysis allowed us to discover brittle star-specific differentiation genes. In conclusion, our results show that the FGF pathway is crucial for skeletogenesis in the brittle star, as in other deuterostomes, and provide evidence for the re-deployment of a developmental gene regulatory module during regeneration.
Highlights
A tempting theory for the evolutionary origins of tissue regeneration suggests it was selected as a secondary by-product of development, sharing many similarities with embryogenesis (Brockes and Kumar, 2008; Morgan, 1901)
To better understand the evolutionary relationships of our A. filiformis genes relative to echinoderm and chordate signalling systems, we used a collection of sequences of Fgf and Vegf ligands and receptors for 41 species spanning all major clades of echinoderms, chordates and non-deuterostome outgroup species such as the pacific oyster (Crassostrea gigas)
The evidence for this is as follows: (1) the expression pattern of fibroblast growth factor (FGF) and VEGF ligands and receptors during development and regeneration allows for the ectodermal-mesodermal tissue interaction, which has been shown to be crucial for skeletogenesis in sea urchin embryos (Röttinger et al, 2008; Adomako-Ankomah and Ettensohn, 2013; Duloquin et al, 2007; Erkenbrack and Petsios, 2017); (2) perturbation of this pathway using the universal pharmacological agent SU5402 resulted in complete inhibition of skeletal spicule formation in both adult arms and embryos; (3) FGF signalling inhibition downregulated the expression of genes involved in biomineralization
Summary
A tempting theory for the evolutionary origins of tissue regeneration suggests it was selected as a secondary by-product of development, sharing many similarities with embryogenesis (Brockes and Kumar, 2008; Morgan, 1901). Many of the components of the genetic network underlying eye development in other species (e.g. otx, six, opsin) have been shown to be expressed and functionally required during adult eye regeneration, others (i.e. pax6) play no role in this context, underlying some important differences (Pineda et al, 2002; Saló et al, 2002). Unravelling the function of signalling pathways and transcription factors (TFs) in development and regeneration can shed light on whether adult organisms with the capability of regeneration re-use developmental gene regulatory networks (GRNs). With new transcriptomic databases (e.g. Iberian ribbed newt, Matsunami et al, 2019; sea anemone, Warner et al, 2018) comparative analysis has shown that embryonic GRNs are partially re-used during adult sea anemone whole-body regeneration. Consistent with the idea that the initiation of regeneration is very different from embryonic development, several genes have been identified that are unique to regeneration (Warner et al, 2019 preprint)
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