Evolutionarily conserved pathways regulating engulfment of apoptotic cells

Abstract

Animal models, such as the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, combined with the powerful approaches of forward and reverse genetics, have greatly contributed to discovering the mechanisms involved in the clearance of dying cells, and indicated a high degree of evolutionary conservation in many of the signal transduction pathways implicated in the uptake of dying cells. This chapter will discuss the studies that led to the isolation of several genes that regulate recognition, uptake, or processing of apoptotic cells, and provide a review of the mutational analysis approaches that revealed the existence of at least two major genetic pathways for phagocytosis of dying cells in C. elegans and mammals. Studies in D. melanogaster have helped identify new players, as well as genes that are homologues of those identified in C. elegans and mammals. The usage of D. melanogaster as one of the model organisms for unraveling the molecular mechanisms of phagocytosis of apoptotic cells will be examined in the light of recently published literature. This chapter will be devoted to a comparative analysis of the biochemical pathways involved in clearance of dead cells, citing studies of phylogenetically diverse multicellular organisms ranging from C. elegans and D. melanogaster, to mammals. © 2009 Springer Netherlands.