page 469) now show that when neural progenitor cells divide, only one progeny cell survives due to asymmetric distribution of pro- and anti-apoptotic factors between daughter cells.
In the developing mouse brain, apoptosis often correlates with the presence of the lipid ceramide and the protein PAR-4, and current models predict that neuronal apoptosis follows soon after cell division. The authors found that, in neuronal progenitors derived from embryonic stem cells, PAR-4 and the intermediate filament protein nestin (a marker of neural progenitors) are asymmetrically distributed after mitosis. One daugher cell inherits high PAR-4 and low nestin levels, and undergoes apoptosis. The other daughter inherits low PAR-4 and high nestin levels, and survives. Ceramide apparently induces apoptosis in the PAR-4–positive cell but not in the nestin-positive cell, possibly through active destruction of ceramide in the surviving daughter. The authors are now trying to determine how ceramide and PAR-4 interact to induce cell death and also hope to identify the mechanism that ensures asymmetric inheritance of PAR-4 and nestin. ▪