The mechanisms by which apoptotic neurons are cleared in developing dorsal root ganglia

Abstract

During development of the nervous system, about half of the neurons generated undergo apoptosis. How these neurons are cleared in the peripheral nervous system was largely unknown. Our lab discovered that clearance in the dorsal root ganglia of mouse embryos was achieved by amateur phagocytes, cells that have other important roles besides phagocytosis. Specifically, the resident glia, satellite glial cell precursors are responsible for engulfing neurons in developing dorsal root ganglia. In addition, we identified the novel receptor Jedi-1, and the purported engulfment receptor MEGF10, as two receptors expressed in the glia that are involved in engulfing apoptotic neurons. Although nothing was known about the signaling mechanisms of Jedi-1 or MEGF10, my dissertation work revealed that both receptors contain two intracellular Immune receptor Tyrosine-based Activation Motifs that are phosphorylated by Src Family Kinases and interact with the non-receptor tyrosine kinase Syk. This interaction was necessary for either receptor to promote phagocytosis. Here, I describe these interactions as well as the importance of apoptotic cell clearance, including possible links to autoimmune disorders.