Development and Disorder of Motor Neurons

Our lab works on the mechanisms underlying the normal development of motor neurons, and how this relates to diseases such as cranial motor neuron disorders and motor neuron disease. Our work on normal development encompasses studies of axon guidance in the ocular motor system which controls eye movement, as well as mechanisms that underlie the formation of neuronal clusters (nuclei) in the brainstem.

We are mapping the development of oculomotor neurons in the developing zebrafish using live imaging, and identifying axon guidance molecules that orchestrate wiring and connectivity in the ocular motor system. In particular, we are investigating the role of the signalling protein alpha2-chimaerin, which we propose to be a key signalling component and integrator of guidance information. Mutations in alpha2-chimaerin cause the human eye movement disorder, Duane Retraction Syndrome. In studies of the cranial motor nuclei, we focus on the role of cadherins, gap junctions and patterns of spontaneous activity in orchestrating the patterns of clustering of functional neuronal groups, using the chick brainstem as a model.  

Our studies on motor neuron disease - amyotrophic lateral sclerosis (ALS) – have focussed on using the chick embryo model to evaluate the effects of mutant forms of the genes TDP-43 and C9ORF72, exploring the idea that dysregulation of the cytoskeleton is a cause of ALS.