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Tuesday, March 31 • 11:15am - 11:30am
Barbara Dietrick: Determining the Genetic Network of Primary Microcephaly Disease (MCPH)

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The developmental disorder, autosomal recessive primary microcephaly (MCPH), results in reduced cerebral cortex development. Mutations in 9 centrosome protein-encoding genes characterize this genetically heterogeneous disease. We used centrosomin (cnn) mutant Drosophila as the model to dissect the disease pathway genetically. Centrosome assembly and microtubule-organizing regulation requires cnn, but cnn mutant adults survive with undefined neuropathology, presumably MCPH-related. To understand this pathology, we used an RNA interference screen to identify cnn mutant modifiers. We discovered that genes controlling oxidative stress, autophagy, and microtubule regulation by the Augmin complex strongly enhanced cnn. We investigated an Augmin complex mutant, dgt4, and found neuroblasts with impaired microtubule organization and reduced Cnn and gamma-tubulin centrosomal recruitment. dgt4 mutants show an early embryo lethality with severe microtubule-organizational defects, including a lack of microtubules attached to kinetochores. These findings suggest microtubule organization, oxidative stress, and autophagy play critical roles in MCPH. Because autophagy requires cnn and microtubules, and the combination of dgt4 and cnn mutations is lethal, I hypothesize Dgt4, and the Augmin complex, also regulate autophagy. This would be an entirely new function for this conserved protein complex. My future project will test this novel concept and contribute valuable information about autophagy regulation and MCPH mechanisms.


Tuesday March 31, 2015 11:15am - 11:30am EDT
Civic Center - Meeting Room A-1 - Ground Floor 505 West Pensacola Street, Tallahassee, FL 32301

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