Hugh Bennett, PhD

We have established a zebrafish animal model of vertebrate development to define the functions of the neurotrophic factor, progranulin. The zebrafish model is amenable to rapid determination of gene function through the use of expression knockdown methods employing antisense technologies. We have shown that knockdown of zebrafish progranulin expression results in premature truncation and inappropriate branching of developing motoneurons. These defects can be rescued by co-administration of zebrafish progranulin or human progranulin mRNA. We have shown that progranulin mRNA rescues the defects resulting from knockdown of Smn1, mutations of which are known to be the underlying cause of spinal muscular atrophy in human patients. The focus of our research is to define the underlying mechanisms that mediate the neurotrophic actions of progranulin in order to develop therapeutic interventions to treat neurodegenerative diseases.