Drosophila Central Nervous System Glia

Abstract

Molecular genetic approaches in small model organisms like Drosophila have helped to elucidate fundamental principles of neuronal cell biology. Much less is understood about glial cells, although interest in using invertebrate preparations to define their in vivo functions has increased significantly in recent years. This review focuses on our current understanding of the three major neuron-associated glial cell types found in the Drosophila central nervous system (CNS)-astrocytes, cortex glia, and ensheathing glia. Together, these cells act like mammalian astrocytes: they surround neuronal cell bodies and proximal neurites, are coupled to the vasculature, and associate closely with synapses. Exciting recent work has shown essential roles for these CNS glial cells in neural circuit formation, function, plasticity, and pathology. As we gain a more firm molecular and cellular understanding of how Drosophila CNS glial cells interact with neurons, it is becoming clear they share significant molecular and functional attributes with mammalian astrocytes.

Figure 1.

Subtypes, positions, and morphology of Drosophila glia. (A) Overview of the Drosophila larval central nervous system (CNS). The neuronal cell cortex (gray) houses all neuronal and most glial cell bodies. CNS synaptic contacts between neurons are found within the neuropil (light gray). Interneurons (IN) (blue) maintain all projections within the neuropil: motorneurons (MN) (red) extend axon terminals into the peripheral muscle field. (Bottom) cross-sectional view of glial subtypes (green). Morphological arrangement in the adult brain is similar. See text for details. (B) Glia at the Drosophila larval neuromuscular junction (NMJ). MN terminals (red) penetrate the muscle; subperineurial glia (light green) enter the space between the MN and muscle. (C) Sensory organs in Drosophila contain at least three glial types: the socket cell, sheath cell, and an axon-associated glial cell. (From Freeman 2012; reprinted, with permission, from the author.)

Figure 2.

Astrocytes in Drosophila. (A) A single cell clone of a larval astrocyte. Green, astrocyte membranes; blue, astrocyte nuclear marker; red, neurons. (From Tasdemir-Yilmaz and Freeman 2014; reprinted, with permission, from the authors.) (B) Astrocyte membrane processes (green) in the larval neuropil associate with nearly all regions of the neuropil containing synapses (red). (From Stork et al. 2014; reprinted, with permission, from the authors.) (C) Drosophila astrocytes recycle neurotransmitters using molecular pathways similar to those in mammals. See text for details. (D) Astrocyte membranes (green) associate closely with tracheal cells (blue), which are gas-filled tubes that allow for gas exchange with the environment. EAAT, excitatory amino-acid transporters; GABA, γ-aminobutyric acid; GAT, GABA transporter; GS, glutamine synthetase.

Figure 3.

Glial engulfment signaling in the adult Drosophila CNS after axotomy. (Step 1) Axonal debris activates signaling downstream from Draper. Activation includes signaling to the nucleus via dJNK/dAP-1 and STAT92E to activate engulfment gene expression, including draper. (Step 2) Glial membranes are recruited to axonal debris via dCed-6 and the Src family kinase cascade and Rac1. The GEFs Drk/Dos/Sos and dCed-12/Mbc/Crk are proposed to act redundantly upstream of Rac1. (Step 3 and Step 4) Internalization of axonal debris and its subsequent acidification for degradation requires Rac1 and the GEFs dCed-12/Mbc/Crk and Drk/Dos.