Significance of Retinoblastoma Protein in Survival and Differentiation of Cerebellar Neurons

During development of the nervous system an excess number of neural progenitor cells are generated and approximately half of these cells are eliminated by programmed cell death (PCD) or apoptosis (Farinelli and Greene, 1996; Jacobson et al., 1997; Oppenheim, 1991; Raff, 1992; Raff et al., 1993). The apoptosis and elimination of the excess number of precursor cells enable the proper synaptic integration of the surviving cells and development of the central nervous system (CNS). Survival of the neurons in the CNS requires trophic support and electrical activity and upon withdrawal or depletion of these factors the neurons undergo apoptosis (Barde et al., 1987; Biffo et al., 1994; D'Mello et al., 1997; D'Mello et al., 1993; D'Mello et al., 2000; Galli et al., 1995; Levi-Montalcini, 1987; Miller and Johnson, 1996). Among the growth factors that support neuronal survival and differentiation are neurotrophic growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 and 4 (NT3 and NT4), insulin and insulin like growth factors (IGF), glial derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF), and ciliary neurotrophic factor (CNTF) (Ardelt et al., 1994; Barde, 1994; de Pablo et al., 1990a; de Pablo et al., 1990b; Ferrari et al., 1989; Ferrer et al., 1998; Hynes et al., 1994; Kalcheim et al., 1987; Knusel et al., 1990; Levi-Montalcini, 1987; Lindholm et al., 1993; Magal et al., 1993; Rabacchi et al., 1999; Rakowicz et al., 2002; Serrano et al., 1990; Tuttle et al., 1994; Zhang et al., 1997).