A major goal in clinical and basic neuroscience is to identify factors that can promote the survival of spinal motor neurons. Despite the identification of several neurotrophic factors that can support motor neurons, we are still incapable of rescuing the majority of motor neurons in vivo. The goal of this proposal is to determine the function of a relatively novel receptor tyrosine kinase, Anaplastic Lymphoma Kinase (ALK), in spinal motor neurons. Based on our preliminary data including the fact ALK is dynamically expressed in spinal motor neurons during the period of programmed cell death (PCD), we hypothesize that ALK promotes the survival of spinal motor neurons. We will test this hypothesis by conducting gain and loss-of-function manipulations of ALK expression chick embryos in ovo and determine the effects on spinal motor neuron survival.
If spinal motor neurons die, paralysis results. Motor neurons die in developmental disorders such as Spinal Muscular Atrophy and in adult-onset disorders such as Amyotrophic Lateral Sclerosis (Lou Gehrig's disease) and following spinal cord injury. We have identified a protein, Anaplastic lymphoma kinase, which is expressed on spinal motor neurons. Our preliminary data indicates that reducing levels of this protein causes the death of spinal motor neurons. The goal of this study is to increase levels of this protein to test whether we can rescue dying spinal motor neurons. This work could lead to novel therapeutics for promoting the survival of motor neurons in neural disease.
