View Program - 63rd Annual Drosophila Research Conference

Authors:
Emily Sterner ¹; Daniel Marenda ²; Jennifer Stanford ¹

Affiliations:
1) Drexel University, Philadelphia, PA; 2) Division of Biological Infrastructure, National Science Foundation, Alexandria, VA

Keywords:
t. other (axon pruning); n. other (chromatin modifiers)

In Drosophila, the chromatin reader Kismet (Kis) is required for proper axon pruning in the developing mushroom body during pupation. Kis is a homolog of the human transcription factor and chormatin reader CHD7. Haploinsufficiency of CHD7 accounts for two-thirds of CHARGE syndrome cases in humans. This neurodevelopmental disorder causes intellectual disability and defects in facial structure and sensory organs. The axon pruning defect caused by loss of Kis in Drosophila can be rescued pharmacologically by HDAC inhibition. Previously, our lab has shown the general HDAC inhibitor SAHA is able to rescue axon pruning defects. To narrow down which HDAC(s) are relevant to the axon pruning process, we are taking a two-pronged approach of: 1) pharmacological inhibition using more specific HDAC inhibitors, and 2) RNAi knockdown of specific HDACs in a Drosophila model for CHARGE syndrome. The Class I HDAC inhibitors Beta-hydroxybutyric acid and sodium butyrate are both able to rescue defects caused by loss of Kis, suggesting that Class I HDACs are relevant to axon pruning and could be putative targets for potential therapeutic for CHARGE syndrome. Follow-up work to confirm the involvement of HDAC1 and/or HDAC3 in the axon pruning process, using RNAi, is ongoing.

Elucidating the interaction between the chromatin reader Kismet and histone deacetylases in the promotion of axon pruning