Development of the central nervous system involves elimination of superfluous neurons through apoptosis and subsequent phagocytosis. In Drosophila, this occurs mainly during three developmental stages: embryogenesis, metamorphosis and emerging adult. Two transmembrane glial phagocytic receptors, SIMU (homolog of the mammalian Stabilin-2) and Draper (homolog of the mammalian MEGF10 and Jedi), mediate glial phagocytosis of apoptotic neurons during embryogenesis. However, less is known about the removal of apoptotic neurons during later stages of development. Here we show that during metamorphosis, Draper plays a critical role in apoptotic cell clearance by glia, whereas SIMU, which is mostly expressed in pupal macrophages outside the brain, is not involved in glial phagocytosis. We found that Draper activates Drosophila c-Jun N-terminal kinase (dJNK) signaling predominantly in the ensheathing glia and astrocytes, where it is required for efficient removal of apoptotic neurons. Our data suggest that besides the dJNK pathway, Draper also triggers an additional signaling pathway capable of removing apoptotic neurons in the pupal brain. This study thus reveals that SIMU unexpectedly is not involved in glial phagocytosis of apoptotic neurons during metamorphosis and highlights the novel role of dJNK signaling in developmental apoptotic cell clearance downstream of Draper.
|Number of pages||13|
|State||Published - Jul 2018|
Bibliographical noteFunding Information:
We would like to thank U. Gaul, B. Jones, D. Bohmann, A. Salzberg, M. Logan, I. Evans, M. Freeman, the Developmental Studies Hybridoma Bank and the Bloomington Stock Center for generously providing fly strains and antibodies. We thank L. Barki-Harrington, Z. Paroush and H. Toledano for comments on the manuscript and the Kurant laboratory members for constructive criticism and support. We also thank E. Suss-Toby and L. Liba at the Interdepartmental Bioimaging facility of the Technion Medical School for excellent technical support and O. Rogovoy for preliminary images in the beginning of the project. We gratefully acknowledge financial support from Israel Science Foundation (grant no. 1872/15).
© 2018 Wiley Periodicals, Inc.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience