DrosophilaCentral 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. Invertebrate preparations have contributed enormously to our understanding of fundamental principles of nervous system biology, including the chemical and electrophysiological basis of the action potential, synaptic vesicle release, neural cell fate specification, and axon pathfinding. This is largely thanks to the high experimental accessibility, ease of culture, rapid growth, and the panoply of molecular genetic tools with which to manipulate individual cells in vivo in organisms like Drosophila and Caenorhabditis elegans. The focus of many neuroscientists has shifted in recent years toward careful exploration of how glial cells participate in nervous system development, neural circuit function and plasticity, and neurological disease. Based on the remarkable success with which invertebrates were used to dissect fundamental aspects of the cell biology of the neuron, interest in the potential of small genetic model organisms to contribute to unraveling the mysteries of glial cells has grown significantly. This article will provide a brief overview of Drosophila glial cell biology, then focus on fly glial cell subtypes that are tightly associated with neurons in the central nervous system (CNS)-astrocytes, ensheathing glia, and cortex glia. A growing body of work argues strongly that these glia share a range morphological and functional features with mammalian astrocytes, and recent molecular studies indicate that conservation of basic glial cell biology extends, perhaps not surprisingly, to the molecular level.

Glia in mammalian development and disease

“…The local control of synapse elimination by microglia relies on the deposition of complement proteins such as C3 and C1q, which are expressed on neurons in an astrocyte-dependent manner, to tag synapses for phagocytosis (Stephan et al, 2012). More recently, it was discovered that astrocytes also directly phagocytose synapses, in both Drosophila and vertebrates, utilizing the Megf10/Draper and Mertk phagocytic receptors (Freeman, 2015;Chung et al, 2015). Mice lacking C1q, or those with astrocytes that lack Megf10 and Mertk, have severe defects in developmental synapse pruning.…”

Monitoring cell-cell contacts in vivo in transgenic animals

“…For example, many recent studies have shown that astrocytes play important roles in synaptic formation and in modulating the functions of neural circuits and behavior in Drosophila (Zwarts et al, 2015;Freeman, 2015) However, as shown in Fig. 3, the interactions between glia and neurons are ubiquitous throughout the nervous system.…”

“…The NRR is folded in such a way that, in the absence of Delta binding, a cleavage site (called S2) is inaccessible to the action of ubiquitous metalloproteases such as Kuzbanian (in Drosophila) or TACE (tumor necrosis factor-α-converting enzyme, or ADAM17, in vertebrates) (Tiyanont et al, 2011). Upon Delta-Notch binding, it is hypothesized that the NRR partially unfolds, thereby increasing the accessibility of the S2 site, and the NRR can then be cleaved by the metalloproteases (Stephenson and Avis, 2012;Tiyanont et al, 2011;Meloty-Kapella et al, 2012;2015). After S2 cleavage, a subsequent cleavage (called S3) by the ubiquitous metazoan gamma-secretase complex occurs in the TMD, within the cell membrane (Brou et al, 2000;Mumm et al, 2000).…”

Investigating Amyloid β toxicity in Drosophila melanogaste

“…Drosophila neurons share similar processes and morphologies as their mammalian counterpart; they fire proper action potentials, they release conserved neurotransmitters from synaptic vesicles through highly conserved mechanisms, and they pass information between neurons at synapses with common protein architecture [246]. The CNS can be further divided into two histological regions; the neuronal cell cortex -composed of all neuronal cell bodies; and the neuropil -the location of axon and dendrite projection and neural circuit formation [247]. To direct expression of a gene of interest to a specific cell type in Drosophila, the Gal4-UAS system is employed (further described in the methodology, Section; Controlling protein expression: the Gal4-UAS system).…”

“…Introduction glial cells have been described from embryonic to adult stage: surface glia -form a layer around the CNS or peripheral nerves; cortex glia -ensheath neuronal cell bodies; and neuropil gliaassociate directly with the neuropil [247], [251]. One of the earliest known markers for cells that will become glia is the transcription factor Reversed polarity (Repo) that is responsible for the differentiation and maintenance of glial cell function.…”