Abstract
Unlike in adult mammals, in regenerative species, appendage amputation is followed by the formation of a highly proliferative and heterogeneous structure called the blastema. The required conditions for its formation are still not completely understood. Paracrine factors produced by neural crest derived cells (NCC) have been proposed to be responsible for blastemal cell proliferation. Moreover, macrophages are recruited to the wound site and could participate to the regeneration process. However, their exact functions and interactions with NCC during regeneration have never been investigated. My thesis project consisted in deciphering those mechanisms using two different models: zebrafish larva caudal fin regeneration and forelimb bud regeneration of the E10.5 mouse embryo. This work allowed us:• In zebrafish larva: to identify two subpopulations of macrophages, to highlight their roles during regeneration, to demonstrate the role of the TNFa/TNFR1 axis in the blastemal cell proliferation and to identify a new foxd3+ NCC population in the caudal fin, which is required for macrophage recruitment, polarization and for blastemal cell proliferation. •In mouse embryo: to identify a regenerative (E10.5) and non-regenerative (E12.5) stage of development, to demonstrate the accumulation of NCC at the wound site in E10.5 embryos and demonstrate the crucial role of NCC during epimorphic regeneration in mammals.