Programmed cell death can be reduced or eliminated in the developing nervous system by the targeted deletion of pro-apoptotic genes or by the overexpression of anti-apoptotic genes. The absence or reduction of PCD can cause serious anatomical malformations but can also result in minimal consequences depending on the gene targeted, neuronal population, and stage of development.  Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 knockout mice which develop exencephaly in the forebrain .   The brainstem, spinal cord, and peripheral ganglia of these mice develop normally, however, suggesting that the involvement of caspases in PCD during development depends on the brain region and cell type.  Knockout or inhibition of apoptotic protease activating factor 1 ( APAF1 ), also results in malformations and increased embryonic lethality.    Manipulation of apoptosis regulator proteins Bcl-2 and Bax (overexpression of Bcl-2 or deletion of Bax) produces an increase in the number of neurons in certain regions of the nervous system such as the retina , trigeminal nucleus , cerebellum, and spinal cord.        However, PCD of neurons due to Bax deletion or Bcl-2 overexpression does not result in prominent morphological or behavioral abnormalities in mice. For example, mice overexpressing Bcl-2 have generally normal motor skills and vision and only show impairment in complex behaviors such as learning and anxiety.    The normal behavioral phenotypes of these mice suggest that an adaptive mechanism may be involved to compensate for the excess neurons.