Oculomotor and trochlear neurons in the developing nervous system respond to molecular guidance cues to innervate target muscles in the eye. Upon reaching their muscle targets, over half of the neurons undergo programmed cell death (PCD), possibly due to competition for limited quantities of neurotrophic factors supplied by the target muscle. The survival of other developing MNs during this period has been shown to be dependent on trophic factors. Studies indicate that various trophic factors increase neuronal survival both in vitro and in vivo, yet treatment with single factors has only proven to promote survival of a percentage (15-30 percent) of the total MNs that undergo normal PCD. One explanation for this, that I hope to test, is that there are sub-populations of MNs each with different trophic requirements and that combinations of the appropriate factors are required for optimal survival. We have devised experiments using the chick embryo to acquire a better understanding of the combinations of trophic factors expressed by different muscles in the chick ocular system, the distribution of the receptors for these trophic factors within the oculomotor and trochlear nuclei and the identity of subnuclei within the oculomotor complex supported by individual trophic factors both in vivo and in vitro. In addition to shedding light on normal development, these studies may also lead to a better understanding of ALS.
