Figure 5: Components of engulfment pathways promote the apoptotic death of the NSMsc.

A molecular model for how components of the engulfment pathways promote NSMsc apoptosis (see text for details). CED-3 caspase activity present in the mother of the NSMsc, the NSMnb, produces a signal (orange arrow) that results in the enrichment of CED-1 on plasma membranes of neighbouring cells apposing the dorsal side of the NSMnb. This signal is independent of ced-8 and PS. We speculate that the dorsal neighbouring cells are primed to receive this signal via a prior symmetry-breaking event, depicted here as somewhat higher expression level of CED-1 in the dorsal neighbours (Supplementary Fig. 7). CED-1 enrichment on the plasma membranes of the dorsal neighbours leads to the activation of components of the two engulfment pathways in these cells. A signal from these neighbours (brown arrow), which is dependent on the functions of components of the two engulfment pathways, subsequently promotes the generation of a gradient of ‘apoptotic potential’ (including a gradient of CED-3 caspase activity) along the dorsal–ventral axis of the NSMnb. During NSMnb division, this gradient causes the unequal segregation of apoptotic potential. As a result, the small dorsal daughter cell, the NSMsc, inherits a higher concentration of this potential. This higher concentration is reflected in a higher level of CED-3 caspase activity and an increase in CED-3 concentration in the NSMsc, both of which contribute to the apoptotic death of the NSMsc within ∼20 min post cytokinesis, at which time point the NSMsc corpse is engulfed by a neighbouring cell (Fig. 2a).