Inhibition of BMP and FGF signaling prior to wound epithelium formation leads to an aberrant regenerative response in teleost fish Poecilia latipinna

Abstract

The BMP and FGF pathways play a pivotal role in the successful regeneration of caudal fin of teleost fish. Individual inhibition of these pathways led to impaired caudal fin regeneration until the pharmacologic inhibitor of FGF (SU5402) and BMP (LDN193189) were metabolized off. Therefore, in the current study both these pathways were inhibited collectively wherein inhibition of BMP and FGF during the wound epithelium formation led to stalling of the process by bringing down the established levels of shh and runx2. In members of the treatment group, it was observed that, each blastema grows crouched rather than linear and the regrown lepidotrichia therefore remain tilted down. Amongst the other irregularities observed, the transition from epithelial to mesenchymal cells was found hindered due to down-regulation of snail and twist, brought about by BMP and FGF inhibition. Compromised expression of Snail and twist deranged the normal levels of cadherins causing disruption in the transition of cells. Lastly, blocking BMP and FGF delayed blastema formation and proliferation due to diminished levels of fgf2, fgf8, fgf10 and bmp6, while casp3 and casp9 levels remained heightened causing accelerated cell death. This study not only highlights the axial role of BMP and FGF pathways in regeneration but also accentuates the collaboration amongst the two. This ingenious coordination of signalling further reinforces the involvement of relaying messenger molecules between these crucial pathways. Summary StatementBMP and FGF collectively control the process of blastema formation in fish and inhibiting them prior to wound epithelium stage leads to irrevocable damage to the regenerating caudal fin.