APOPTOSIS IN THE DEVELOPING CNS

In this review, apoptosis during normal development of the CNS and abn ormal apoptosis inducing hydrocephaly and arhinencephaly will be discu ssed. 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 ab normal apoptosis inducing abnormal brain morphogenesis, we will discus s genetically induced arhinencephaly and hydrocephaly. It was suggeste d that apoptosis of the precursor mitral cells in the anlage of the ol factory 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 muta nt arhinencephalic mouse brain (Pdn/Pdn). Thus, sequential apoptosis o f the precursor neurons and sequential manifestation of the brain abno rmalities were Proposed in arhinencephalic mutant mouse embryos and al so in the arhinencephalic brains induced experimentally by fetal laser surgery exo utero. Meanwhile, it was speculated that the Gli3 gene, m utation of which is responsible for the arhinencephaly in Pdn/Pdn mice , might play a role in mesenchymal programmed cell death during develo pment.