Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Developmental Neuroscience | Molecular and Cellular Neuroscience
Precise neural circuit assembly is achieved by initial overproduction of neurons and synapses, followed by refinement through elimination of exuberant neurons and synapses. Glial cells are the primary cells responsible for clearing neuronal debris, but the cellular and molecular basis of glial pruning is poorly defined. Here we show that Drosophila larval astrocytes transform into phagocytes through activation of a cell-autonomous, steroid-dependent program at the initiation of metamorphosis and are the primary phagocytic cell type in the pupal neuropil. We examined the developmental elimination of two neuron populations-mushroom body (MB) gamma neurons and vCrz(+) neurons (expressing Corazonin [Crz] neuropeptide in the ventral nerve cord [VNC])-where only neurites are pruned or entire cells are eliminated, respectively. We found that MB gamma axons are engulfed by astrocytes using the Draper and Crk/Mbc/dCed-12 signaling pathways in a partially redundant manner. In contrast, while elimination of vCrz(+) cell bodies requires Draper, elimination of vCrz(+) neurites is mediated by Crk/Mbc/dCed-12 but not Draper. Intriguingly, we also found that elimination of Draper delayed vCrz(+) neurite degeneration, suggesting that glia promote neurite destruction through engulfment signaling. This study identifies a novel role for astrocytes in the clearance of synaptic and neuronal debris and for Crk/Mbc/dCed-12 as a new glial pathway mediating pruning and reveals, unexpectedly, that the engulfment signaling pathways engaged by glia depend on whether neuronal debris was generated through cell death or local pruning.
Rights and Permissions
© 2014 Tasdemir-Yilmaz and Freeman; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (seehttp://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
DOI of Published Version
Genes Dev. 2014 Jan 1;28(1):20-33. doi: 10.1101/gad.229518.113. Epub 2013 Dec 20. Link to article on publisher's site
Genes and development
Tasdemir-Yilmaz OE, Freeman MR. (2014). Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. GSBS Student Publications. https://doi.org/10.1101/gad.229518.113. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1964