Abstract
Epimorphic regeneration resulting in the restoration of a tissue, organ or appendage identical to the original one in terms of mass structure and function is possible in some vertebrates such as zebrafish or salamander but is a rare event in mammals. Understanding the mechanisms associated with this process is crucial and promising for various therapeutic applications in the field of regenerative medicine. One of the key steps in this regeneration process is the formation of a transient, hyperproliferative and heterogeneous structure called blastema. Macrophages are known to participate to the formation of this structure though a tightly regulated recruitment and activation kinetic. However, their mechanisms of action in real time during the regeneration have been poorly studied. During my thesis project, I have used the 3 days post-fertilization zebrafish larva model able to regenerate its caudal fin within 72 hours to identify the mechanisms that orchestrate the macrophage response during epimorphic regeneration. In this context, my project aimed at studying various cellular and molecular processes responsible for the macrophage recruitment and activation during the caudal fin regeneration of the zebrafish larva, both in an infectious and non-infectious environment. This work allowed us to highlight:- the existence of a cellular dialogue between cells derived from the neural crest and macrophages via the NRG1/ErbB pathway allowing macrophage recruitment and activation.- the role of glycolysis and lactate metabolism on macrophage recruitment, activation and regeneration.- the impact of an infectious pathogenic environment frequently present in injured tissue, on macrophage recruitment, activation and regeneration.