Digit regeneration in mice is stimulated by sequential treatment with FGF2 and BMP2

Digit amputation in mice is non-regenerative and we show that blastema formation and digit regeneration is stimulated by sequential treatment with FGF2 and BMP2. FGF2 act as a priming agent to stimulate blastema formation and BMP2 induces differentiation of the blastema to regenerate the amputated phalangeal element. FGF2 induced blastema cells are positionally re-specified and re-programmed to regenerate the amputated distal skeletal structure. FGF2→BMP2 treatment also stimulates the regeneration of the amputated sesamoid bone and joint complex but in a blastema-independent manner. Coordination of the blastema-dependent and blastema-independent responses result in the complete regeneration of all amputated skeletal structures. The data indicates that blastema-dependent regeneration involves a re-development response, displaying characteristics of dedifferentiation and embryonic development. Induced regeneration demonstrates the availability of regeneration competent cells and provides evidence that of FGF and BMP signaling is responsible for triggering a regenerative outcome at wounds that heal by fibrosis. One Sentence Summary : FGF2 and BMP2 stimulates digit regeneration in mice