Development of the cerebral cortex: VIII. Apoptosis: neuronal Hari-Kari.

It is a curious fact of CNS development that more than half of the neurons and glial cells that are born are destined to die. The elimination of these cells is accomplished by an orderly type of cellular suicide called programmed cell death or apoptosis (pronounced ap-a-tow’-sis). Although developmental biologists have long recognized the role of programmed cell death in metamorphosis and in sculpting vertebrate digits, the recent upsurge in interest in this field stems from discoveries showing that it is an active genetic process that is regulated via multiple signaling pathways. Apoptosis has been described for nearly every cell type in the body, and it occurs in diverse species from plants up the evolutionary tree to humankind. It is a critical factor in the development of the cerebral cortex. In the nervous system, final cell number is the sum of progressive developmental events such as neurogenesis and regressive events such as cell death. As described in earlier columns, CNS cells are generated during specific times of development within proliferating layers called the ventricular and subventricular zones. These layers surround the hollow core of the neural tube. After their final division, young neurons migrate away from these zones and maintain their postmitotic state for the life of the organism. Recent work has shown that during periods of cell genesis and the establish-