Spatiotemporal distribution of dying neurons during early mouse development

Apoptosis is a critical cellular event during several stages of neuronal de velopment. Recently, we have shown that biotinylated annexin V detects apop tosis in vivo in various cell lineages of a wide range of species by bindin g to phosphatidylserines that are exposed at the outer leaflet of the plasm a membrane. In the present study, we tested the specificity by which annexi n V binds apoptotic neurons, and subsequently investigated developmental ce ll death in the central and peripheral nervous system of early mouse embryo s at both the cellular and histological level, and compared the phagocytic clearance of apoptotic neurons with that of apoptotic mesodermal cells. Our data indicate: (i) that biotinylated annexin V can be used as a sensitive marker that detects apoptotic neurons, including their extensions at an ear ly stage during development; (ii) that apoptosis plays an important part du ring early morphogenesis of the central nervous system, and during early qu antitative matching of brain-derived neurotrophic factor and neurotrophic f actor 3 responsive postmitotic large clear neurons in the peripheral gangli a with their projection areas; and (iii) that apoptotic neurons are removed by a process that differs from classical phagocytosis of non-neuronal tiss ues.