The apoptosis cascade - morphological and immunohistochemical methods for its visualization

Apoptosis is involved in morphogenesis of embryonic tissues as well as in h omeostasis of adult organs and tissues. It is the main process by which org ans maintain cell mass and at the same time eliminate excess and aged cells that have lost their functional importance. The typical morphological sign s of apoptosis (cellular shrinkage, membrane blebbing, nuclear condensation and fragmentation) are the final results of a complex biochemical cascade of events, some of which are inextricably linked to the process of differen tiation. Studies that analyze all stages of this cascade, rather than the f inal morphological stages of apoptotic death, are essential in order that s pecific link(s) between differentiation and apoptosis are appreciated. This review outlines the main stages of the apoptosis cascade together with cur rent methods for their morphological visualization. Starting with (a) recep tors and ligands known to induce apoptosis, we continue with (b) early init iator stages of apoptosis and (c) proteins regulating and potentially inhib iting further progression of the cascade, into (d) irreversible execution s tages of the cascade, and finally (d) the morphological events of apoptotic death. For each stage we present those aspects of the biochemical backgrou nd that are morphologically relevant, together with proven methods for thei r visualization. We offer technical advice at each stage based upon our exp erience of studying differentiation and apoptosis in human placental tropho blast.