Mechanism Explains Selective Pruning of Neuronal Stem Cells

Researchers have identified a mechanism that triggers the death of a portion of the stem cell population in the developing brain, thereby limiting the number of cells to an appropriate number and location for the brain to develop in a normal fashion.

Investigators from the Medical College of Georgia (Atlanta, USA) and the University of Georgia (Atlanta, USA) found that initiation of apoptosis depended on the presence of two triggering factors, elevated levels of the lipid ceramide and expression of the protein prostate apoptosis response 4 (PAR-4).

By employing specific antibodies, the investigators showed that potentially apoptotic cells stained for proliferating cell nuclear antigen (a nuclear mitosis marker protein), but not for nestin (a marker for maturing nerve cells). In mitotic cells, asymmetric distribution of PAR-4 and nestin resulted in one nestin(-)/PAR-4(+) daughter cell, in which ceramide elevation induced apoptosis. The other cell was nestin(+), but PAR-4(-), and was not apoptotic. This asymmetric distribution of PAR-4 coupled with a simultaneous elevation of endogenous ceramide provided a possible mechanism underlying asymmetric differentiation and apoptosis of neuronal stem cells in the developing brain. These findings were published July 28, 2003, in the online edition of the Journal of Cell Biology.

"During normal development in the central nervous system there is a great deal of cell death that occurs that seems to be required to create the final shape and structure of the brain,” explained senior author Dr. Brian G. Condie, a developmental neurobiologist at the University of Georgia. "One of the ideas behind why there is an excess of cells generated during development is that it may be a mechanism for compensating for environmental stresses or other types of stresses that an embryo may encounter during development. So you actually generate an excess of the cells you need and then prune those cells back to an appropriate number and location for the brain to develop in a normal fashion.”





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