Ensheathing Glia Function as Phagocytes in the Adult Drosophila Brain

Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605-2324, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2009; 29(15):4768-81. DOI: 10.1523/JNEUROSCI.5951-08.2009
Source: PubMed


The mammalian brain contains many subtypes of glia that vary in their morphologies, gene expression profiles, and functional roles; however, the functional diversity of glia in the adult Drosophila brain remains poorly defined. Here we define the diversity of glial subtypes that exist in the adult Drosophila brain, show they bear striking similarity to mammalian brain glia, and identify the major phagocytic cell type responsible for engulfing degenerating axons after acute axotomy. We find that neuropil regions contain two different populations of glia: ensheathing glia and astrocytes. Ensheathing glia enwrap major structures in the adult brain, but are not closely associated with synapses. Interestingly, we find these glia uniquely express key components of the glial phagocytic machinery (e.g., the engulfment receptor Draper, and dCed-6), respond morphologically to axon injury, and autonomously require components of the Draper signaling pathway for successful clearance of degenerating axons from the injured brain. Astrocytic glia, in contrast, do not express Draper or dCed-6, fail to respond morphologically to axon injury, and appear to play no role in clearance of degenerating axons from the brain. However, astrocytic glia are closely associated with synaptic regions in neuropil, and express excitatory amino acid transporters, which are presumably required for the clearance of excess neurotransmitters at the synaptic cleft. Together these results argue that ensheathing glia and astrocytes are preprogrammed cell types in the adult Drosophila brain, with ensheathing glia acting as phagocytes after axotomy, and astrocytes potentially modulating synapse formation and signaling.

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    • "memory tasks ( Han et al . , 2013 ; Windrem et al . , 2014 ) . This was an important observation , especially because astrocyte morphology and function appear some - what evolutionarily conserved : in Drosophila , astrocytes also form a dense meshwork of processes that wrap around syn - apses and are essential for animal development and survival ( Doherty et al . , 2009 ; Stork et al . , 2014 ) . Such observations suggest a reasonable scope for the extrapolation of astroglial physiology from experimental animals ( mainly rodents ) to humans ."
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    • "Since then, many studies have focused on the distinct function of these two subtypes of glia. It was reported that ensheathing glia expressed engulfment receptors and phagocytosed degenerated axons, and cell death-triggered olfactory circuit plasticity was mediated through ensheathing glia, but astrocyte-like glial cells were not involved in these processes (Doherty et al., 2009; Kazama et al., 2011). In addition, astrocyte-like glia communicated with clock neurons and regulated A B C Fig. 6 "
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    • "Ziegenfuss and colleagues (2008) then showed that Shark/Syc and Src42A are required for signaling events downstream of Draper, which argued that Draper signaling was molecularly similar to mammalian immune signaling during engulfment events. Subsequent studies identified the specific subtypes of fly glia that engulfed axonal debris (Doherty et al. 2009), the molecular complex required for activation of phagolysosomal activity and internalization of axonal debris (Ziegenfuss et al. 2012), and the mechanism by which Draper also acts to terminate glial responses to injury (Logan et al. 2012). At the same time, a number of studies explored the molecular basis of axon degeneration. "
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