Because of their differential expression, homophilic affinity and synaptic localization, the clustered Pcdhs have been proposed to be the “synaptic adhesive code” that specifies neuronal connectivity (Junghans et al., 2005; Serafini, 1999; Shapiro and Colman, 1999). Therefore, an intuitively attractive hypothesis for the concurrent neuronal apoptosis and synaptic defects in Pcdhg deficient mice is that the loss of function of Pcdhgs leads to synaptic loss, which in turn compromises neuronal survival (Junghans et al., 2005; Prasad et al., 2008). However, several observations reported here strongly argue against this possibility. 1) Deletion of Pcdhg cluster does not lead to a general loss of synapses. Instead, we found that Pcdhg deficiency differentially influences cholinergic, glutamatergic, GABAergic and glycinergic synapses on motor neurons. Therefore, the synapse loss observed using generic synaptic markers only reflects the additive effects of alterations in multiple types of synapses, and loss of synaptic contacts, at the very least, cannot explain the loss of neurons in all cases; 2) Consistent with the observations in the retina, the Pcdhgdel/del;Bax−/− and Pcdhgtcko/tcko;Bax−/− compound mutants showed preservation of stretch reflex circuits and
