Mice that are deficient for Apaf1 or caspase-9 are defective for cytochrome dependent apoptosis. Apoptosis is a critical event in development, allowing excess brain cells to be weeded out. The extent of brain overgrowth and the size of the cranial protrusions indicate that the pruning process in the developing brain must be massive. The dramatic effects of the deficiencies of Apaf1 and caspase-9 suggest that the cytochrome c-dependent apoptotic pathway the intrinsic pathway must be critically important in brain development.