The role of p53 in regenerating necrotic tissue

Strokes, infections, and injuries often lead to widespread necrotic tissue death. Necrosis is a form of lytic cell death that can occur in every multicellular organism, resulting in complex and poorly understood tissue outcomes. Unlike programmed cell death, such as apoptosis, the uncontrolled release of cellular contents during necrosis severely impacts neighboring tissue. However, we know very little about the mechanisms underlying these events and their outcomes. Understanding this phenomenon is challenging because of the uncontrolled and variable nature of necrosis. However, our lab has pioneered research into necrosis using Drosophila melanogaster, the common fruit fly, which has significant regenerative capabilities even in the face of different types of cell death, including necrosis. Our lab has developed a sophisticated genetic manipulation system called Duration And Location (DUAL) Control, which we use to study cell death and regeneration within the larval precursor of the adult wing, known as the wing imaginal disc. We found that necrotic cell death leads to caspase activation, normally associated with apoptotic cell death, in the surrounding tissue. We called these cells “Necrosis-induced caspase-positive cells” (NiCP) . However, NiCP do not behave like normal apoptotic cells, fail to undergo cell death, and most importantly appear to be essential for successful regeneration. My preliminary data shows that NiCP formation and function are regulated by p53. Uncovering p53’s role in necrosis-induced regeneration may reveal unique functions and lead to innovative therapies for necrotic tissue damage, potentially improving the prevention, diagnosis, and treatment of various conditions.