The researchers focused on a particular cell lineage in the C. elegans embryo, the so-called NSM lineage. The NSM mother cell divides asymmetrically, resulting in two daughter cells of unequal size, with the smaller one surviving for a very short time. "Up until now, it was believed that the apoptotic machinery is activated only in the smaller daughter cell after the division of the mother cell," Conradt explains. "But we found that it is already activated – at least to a certain degree - in the mother cell. Moreover, in this pre-activated state, the apoptotic machinery produces a signal that activates the engulfment pathways in specific neighboring cells. And these adjacent cells then help the mother cell to polarize and to concentrate the cell-death protein CED-3 (...). Thus, the mother cell determines the cell death fate of the smaller daughter by asymmetric segregation of CED-3."
CED-3 is known to function as a killer factor, which activates the apoptotic program. "So, prior to cell division, the mother cell is already actively engaged in 'assisting' the smaller daughter cell to kill itself, by supplying it with an overdose of cell-death-promoting factors," Conradt concludes. She and her colleagues now plan to analyze this process further and to ask whether it also takes place in mammalian tissues or stem cells. "Unequal segregation of resources may be especially important in stem cells, which also divide asymmetrically, as factors that may be deleterious to the surviving cell can be disposed of by loading them into the daughter cell that is fated to die," says Conradt.
The research group of Prof. Conradt focuses on the molecular biology of apoptosis, because it plays a crucial role in health maintenance, as errors in the process can be harmful for the whole organism. Many disorders have been linked to errors in the control of apoptosis, like certain cancers, neurodegenerative disorders and autoimmune diseases. Thus a better understanding of the mechanisms underlying apoptosis could in the future help to identify targets for the development of new therapeutics.
(© Ludwig Maximilians University of Munich LMU, AcademiaNet)