Thus, multiple neurotrophins are probably necessary for the survival of proprioceptive neurons in the trigeminal nervous system. This suggestion can be partly supported by our previous finding that the exogenous BDNF prevents cell death of Mes5 neurons after neonatal masseteric nerve transection [45]. It is likely that the neurotrophin dependency of proprioceptive neurons is different in the spinal and trigeminal nervous systems. Brn-3a/Brn-3.0 is a member of the POU family of transcription factors expressed by neurons [46], [47], [48] and [49]. This factor protects neurons from their cell death and stimulates outgrowth of neuronal processes [50], [51] and [52]. Targeted deletion of the

Brn-3a gene in mice has little or no effect on the number of sensory neurons in the DRG [53]. However, loss of Brn-3a causes a marked reduction of sensory neurons in the TG; only 30% of the normal see more GSK1210151A concentration complement of neurons survive until birth [53] and [54].

By cell size analysis, the proportion of small neurons markedly increases while that of medium-sized and large neurons significantly decreases in the TG of Brn-3a knockout mice [55]. Thus, it is likely that Brn-3a deficiency predominantly causes the cell death of medium-sized and large TG neurons. Our immunohistochemical studies have indicated that Brn-3a is necessary for the development of nociceptors and low threshold-mechanoreceptors Bay 11-7085 in the TG (Table 2) [55] and [56]. The loss of Brn-3a reduces

the number of medium-sized CGRP-containing neurons [56]. In Brn-3a knockout mouse, medium-sized and large TRPV2-containing neurons disappear whereas small TRPV1-containing neurons remain unchanged (Table 2) [55] and [57]. In addition, a 63% decrease of parvalbumin-containing TG neurons is detected (Table 2) [56]. In the Brn-3a knockoutvibrissa, parvalbumin-containing endings are lost and Merkel endings are reduced. Thus, it is suggested that primary nociceptors and mechanoreceptors with medium-sized and large cell bodies in the TG require Brn-3a for their survival. On the other hand, the number of small TG neurons which contain CGRP, calbindin D-28k or calretinin is increased by the loss of Brn-3a [56]. Brn-3a may also have a function to suppress the expression of these neurochemical substances in small TG neurons. The trigeminal motor nucleus contains abundant motoneurons in wild-type and Brn-3a knockout mice [58]. In the Mes5 of wild-type mice, many proprioceptors that contain parvalbumin are also observed. In Brn-3a knockout mice, however, parvalbumin-containing Mes5 neurons cannot be detected (Table 2) [58]. Therefore, Brn-3a is probably required for the survival of proprioceptors but not motoneurons in the trigeminal nervous system. Dystoninis known as Bullous Pemphigoid Antigen 1 (Bpag1) which is a member of the plakin family of high molecular weight cytoskeletal linker proteins [59].