progranulin • zebrafish • motor neuron development • protein structure and function • high-performance liquid chromatography (HPLC)
We are using the zebrafish to study the role that a family of tissue growth factors (the granulins) plays in early vertebrate development. In mammals, over-expression of the progranulin gene has been shown to contribute to the progression of many cancers. In contrast, progranulin gene under-expression resulting from the loss of one allele has been shown to lead to a form of frontotemporal dementia in human patients. We have shown that in the zebrafish, the granulins are members of a multi-gene family. Knockdown of progranulin gene expression leads to disruption of organ formation including the central nervous system. One of the more tractable consequences of knockdown of progranulin in zebrafish is disruption of normal caudal motor neuron development. We are using this developmental assay to define the mechanism of action of progranulin and the development of novel therapeutics with neuroprotective properties.
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