Dataset Information

The glia of the adult Drosophila nervous system.

ABSTRACT: Glia play crucial roles in the development and homeostasis of the nervous system. While the GLIA in the Drosophila embryo have been well characterized, their study in the adult nervous system has been limited. Here, we present a detailed description of the glia in the adult nervous system, based on the analysis of some 500 glial drivers we identified within a collection of synthetic GAL4 lines. We find that glia make up ?10% of the cells in the nervous system and envelop all compartments of neurons (soma, dendrites, axons) as well as the nervous system as a whole. Our morphological analysis suggests a set of simple rules governing the morphogenesis of glia and their interactions with other cells. All glial subtypes minimize contact with their glial neighbors but maximize their contact with neurons and adapt their macromorphology and micromorphology to the neuronal entities they envelop. Finally, glial cells show no obvious spatial organization or registration with neuronal entities. Our detailed description of all glial subtypes and their regional specializations, together with the powerful genetic toolkit we provide, will facilitate the functional analysis of glia in the mature nervous system. GLIA 2017 GLIA 2017;65:606-638.

SUBMITTER: Kremer MC

PROVIDER: S-EPMC5324652 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The glia of the adult Drosophila nervous system.

Kremer Malte C MC Jung Christophe C Batelli Sara S Rubin Gerald M GM Gaul Ulrike U

Glia 20170130 4

Glia play crucial roles in the development and homeostasis of the nervous system. While the GLIA in the Drosophila embryo have been well characterized, their study in the adult nervous system has been limited. Here, we present a detailed description of the glia in the adult nervous system, based on the analysis of some 500 glial drivers we identified within a collection of synthetic GAL4 lines. We find that glia make up ∼10% of the cells in the nervous system and envelop all compartments of neur ...[more]

PMID: 28133822

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Project description:Neurodegenerative disorders affect millions of adults worldwide. Neuroglia have become recent therapeutic targets due to their reparative abilities in the recycling of exogenous neurotoxins and production of endogenous growth factors for proper functioning of the adult nervous system (NS). Since neuroglia respond effectively to stimuli within in vivo environments on the micron scale, adult glial physiology has remarkable synergy with microscale systems. While clinical studies have begun to explore the reparative action of Müller glia (MG) of the visual system and Schwann Cells (ShC) of the peripheral NS after neural insult, few platforms enable the study of intrinsic neuroglia responses to changes in the local microenvironment. This project developed a low-cost, benchtop-friendly microfluidic system called the glia line system, or gLL, to advance the cellular study needed for emerging glial-based therapies. The gLL was fabricated using elastomeric kits coupled with a metal mold milled via conventional computer numerical controlled (CNC) machines. Experiments used the gLL to measure the viability, adhesion, proliferation, and migration of MG and ShC within scales similar to their respective in vivo microenvironments. Results illustrate differences in neuroglia adhesion patterns and chemotactic behavior significant to advances in regenerative medicine using implants and biomaterials, as well as cell transplantation. Data showed highest survival and proliferation of MG and ShC upon laminin and illustrated a four-fold and two-fold increase of MG migration to dosage-dependent signaling from vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), respectively, as well as a 20-fold increase of ShC migration toward exogenous brain-derived neurotrophic factor (BDNF), compared to media control. The ability to quantify these biological parameters within the gLL offers an effective and reliable alternative to photolithography study neuroglia and their local ranges on the tens to hundreds of microns, using a low-cost and easily fabricated system.

Project description:The Drosophila nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix are just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the Drosophila larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions to uphold the structure of the glia-extracellular matrix sheath. Knockdown of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximity to integrin at the glial membrane, and that expression of the extracellular integrin-binding domain of Basigin is sufficient to rescue peripheral glial compression. We also found that a reduction in expression of integrin at the membrane rescues the ventral nerve cord shortening, peripheral glial compression, and locomotor phenotypes, and that reduction in the integrin-binding protein Talin can partially rescue glial compression. These results identify Basigin as a potential negative regulator of integrin in the glia, supporting proper glial and extracellular matrix ensheathment of the nervous system.SIGNIFICANCE STATEMENT The glial cells and extracellular matrix play important roles in supporting and protecting the nervous system, but the interactions between these components have not been well characterized. Our study identified expression of a conserved Ig superfamily protein, Basigin, at the glial membrane of Drosophila where it associates with the integrin-based focal adhesion complexes to ensure proper ensheathment of the CNS and PNS. Loss of Basigin in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system.

Dataset Information

The glia of the adult Drosophila nervous system.

Publications

The glia of the adult Drosophila nervous system.

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