Target dependence of motoneurones

The role of the peripheral target in the maintenance of motoneurones has been highlighted recently by reports that certain neurotrophic factors can promote motoneuronal survival (Yan, Elliot & Snider, 1992; Oppenheim et al., 1992; Sendtner et al., 1992a; Henderson et al., 1993; Lindsay, 1995). While these studies have considerable potential to advance our understanding of the mechanisms underlying the regeneration and degeneration of motoneurones, they are concerned principally with the developing neuromuscular system and with motoneurones in vitro. This chapter considers briefly the effect of age on the target-dependence of motoneurones in vivo.

Motoneurones in developing and neonatal animals

The critical role of the periphery for developing motoneurones was highlighted by Hamburger (1934, 1977), who showed that limb bud removal in chick embryos increased the number of motoneurones lost above that expected for programmed cell death, while grafting a supernumerary limb reduced this number. Studies of the molecular nature of the interaction between motoneurones and their targets were facilitated by the serendipitous discovery of nerve growth factor (NGF), a target-derived polypeptide promoting the maintenance and survival of neural-crest-derived neurones and able to ameliorate the retrograde effects of axotomy on them (Hamburger & Levi-Montalcini, 1949; Rich et al., 1987; Purves, 1988). While NGF was not found to have trophic effects on motoneurones (Oppenheim, Maderut & Tytell, 1982; Yan et al., 1988), characterization of its molecular structure allowed the subsequent identification of three other structurally related polypeptides (neurotrophins) which do (see Mudge, 1993, for review).