Drosophila epidermal cells function as phagocytes to clear degenerated dendrites during dendrite pruning. Chun Han, Yuanquan Song, Denan Wang, Lily Jan, Yuh-Nung Jan. Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, Univ California, San Francisco, San Francisco, CA.

   During the development of the nervous system, many neurons remodel their dendritic arbors to reshape neural circuitry. The excessive dendrites are pruned and go through degeneration programs during the dendrite remodeling. Prompt clearance of the degenerated dendrites from surrounding tissues is critical for maintenance of homeostasis and prevention of inflammatory responses. How the degenerated dendrites are cleared by phagocytosis and degraded in phagocytes is poorly understood. To address this question, we studied the clearance of degenerated dendrites during dendrite pruning of Drosophila dendritic arborization (da) neurons. By using the GEEM (gene expression with an independent enhancer-driven cellular marker) strategy to manipulate individual extraneural tissues that interact with da dendrites, we found that Drosophila epidermal cells, instead of hemocytes, are the main phagocytes in the engulfment and degradation of degenerated dendrites. To further analyze how dendrite debris is degraded in epidermal cells, we created a series of dendritic markers to trace the maturation of dendrite-derived phagosomes and established the first in vivo model system in Drosophila for analyzing phagosome maturation. We show that engulfment of degenerated dendrites by epidermal cells is mediated by scavenger receptor Drpr, and two members of CD36 family encoded by croquemort (crq) and debris buster (dsb) act at distinct stages of phagosome maturation. Lastly, we found that the phagocytic activity of epidermal cells facilitates dendrites fragmentation, demonstrating the coordination between neurons and phagocytes during dendrite degeneration.