Taken together, these observations strongly suggest that neuronal cell death in Pcdhgtcko/tcko and Pcdhgdel/del mutants does not result from synaptic defects, but occurs independently due to the lack of C-type genes. Although we cannot rule out the possibility that synaptic or wiring defects may have contributed to the apoptosis of certain types of neurons, it cannot account for the massive cell death observed. In fact, loss of synaptic partners does not usually lead to apoptosis, and even grossly aberrant synaptic connections created experimentally are sometimes maintained without affecting the survival of source neurons (Buss et al., 2006; Oppenheim, 1991).
