Cynthia Corley Mastick: Slit fragments generate diversity in axon guidance and cell signaling
Title
Slit fragments generate diversity in axon guidance and cell signaling
Mentor
Department
Biosketch
I have a long-standing interest in the biochemistry and cell biology of adipose tissue and how this tissue is affected in diabetes and metabolic disease. My current research is focused on sympathetic innervation in adipose tissue. Mobilization of fat depots is triggered via direct stimulation of adipocytes by sympathetic nerves. The extent of innervation, and thus the ability to mobilize stored fat, is extensively and rapidly remodeled in response to environmental (e.g. cold-exposure) and pathophysiological stimuli. We are studying the signals that control this remodeling, with the hope to reverse the defects in metabolic disease.
Project overview
My current research is a collaboration with T. Kidd, Ph.D., and G. Mastick, Ph.D., in the Department of Biology at the University of Nevada, Reno, to explore the role of a canonical axon guidance cue, Slit2, in the coordinated responses of neurons, blood vessels, immune cells/macrophages, and surrounding tissues (fat/liver) to changes in metabolism. Our group is focused on the role that proteolytic cleavage of Slit2 plays in this process. This remains a controversial, and very exciting question in developmental neurobiology as well as in metabolism. Full length Slits act as negative or repellent signals for axons. Cleavage of Slit2 is a mechanism to locally convert an inhibitory signal into a positive, stimulatory signal for axons. We have accumulating evidence that many cell types respond to both the full length Slit2 and the two resulting proteolytic fragments, which would allow for the coordinated regulation of many cell types within tissues. Our current research project is focused on identifying the specific cell surface signaling receptors that bind to the different fragments of Slit2 and transduce the signals into the cells. Techniques used include care and breeding of mutant mouse lines, embryo dissection, in vitro cell and neuron culture, expression of recombinant Slit2 proteins and receptors, western blotting, and immunofluorescence.
Pack Research Experience Program information and application