Apoptosis in the developing CNS.

In this review, apoptosis during normal development of the CNS and abnormal apoptosis inducing hydrocephaly and arhinencephaly will be discussed. As the prominent sites of apoptosis during normal development of the CNS, we focused on the area of fusion of the neural plate to form the neural tube, the developing rhombomeres, and neuronal loss in the CNS during embryogenesis and postnatal development. As examples of abnormal apoptosis inducing abnormal brain morphogenesis, we will discuss genetically induced arhinencephaly and hydrocephaly. It was suggested that apoptosis of the precursor mitral cells in the anlage of the olfactory bulb was induced by non-innervation of olfactory neurons, and apoptosis of the precursor neurons in the pyriform cortex was induced by the non-innervation caused by the death of mitral cells in the mutant arhinencephalic mouse brain (Pdn/Pdn). Thus, sequential apoptosis of the precursor neurons and sequential manifestation of the brain abnormalities were proposed in arhinencephalic mutant mouse embryos and also in the arhinencephalic brains induced experimentally by fetal laser surgery exo utero. Meanwhile, it was speculated that the Gli3 gene, mutation of which is responsible for the arhinencephaly in Pdn/Pdn mice, might play a role in mesenchymal programmed cell death during development.