Multifunctional glial support by Semper cells in the Drosophila retina.

Mark A Charlton-Perkins,Edward D Sendler,Elke K Buschbeck,Tiffany A Cook,Donald Ready

doi:10.1371/journal.pgen.1006782

Abstract

Glial cells play structural and functional roles central to the formation, activity and integrity of neurons throughout the nervous system. In the retina of vertebrates, the high energetic demand of photoreceptors is sustained in part by Müller glia, an intrinsic, atypical radial glia with features common to many glial subtypes. Accessory and support glial cells also exist in invertebrates, but which cells play this function in the insect retina is largely undefined. Using cell-restricted transcriptome analysis, here we show that the ommatidial cone cells (aka Semper cells) in the Drosophila compound eye are enriched for glial regulators and effectors, including signature characteristics of the vertebrate visual system. In addition, cone cell-targeted gene knockdowns demonstrate that such glia-associated factors are required to support the structural and functional integrity of neighboring photoreceptors. Specifically, we show that distinct support functions (neuronal activity, structural integrity and sustained neurotransmission) can be genetically separated in cone cells by down-regulating transcription factors associated with vertebrate gliogenesis (pros/Prox1, Pax2/5/8, and Oli/Olig1,2, respectively). Further, we find that specific factors critical for glial function in other species are also critical in cone cells to support Drosophila photoreceptor activity. These include ion-transport proteins (Na/K+-ATPase, Eaat1, and Kir4.1-related channels) and metabolic homeostatic factors (dLDH and Glut1). These data define genetically distinct glial signatures in cone/Semper cells that regulate their structural, functional and homeostatic interactions with photoreceptor neurons in the compound eye of Drosophila. In addition to providing a new high-throughput model to study neuron-glia interactions, the fly eye will further help elucidate glial conserved "support networks" between invertebrates and vertebrates.

Highlights

Glia have been recognized as a major and heterogeneous non-neuronal cell type in the nervous system for more than 150 years, but their chief homeostatic and regulatory roles in nervous system development and maintenance have only recently emerged [1,2,3,4]
Using cell-restricted transcriptome analysis, here we show that the ommatidial cone cells in the Drosophila compound eye are enriched for glial regulators and effectors, including signature characteristics of the vertebrate visual system
Using cell-specific molecular genetic approaches, we demonstrate that cone cells (CCs) share molecular, functional, and genetic features with both vertebrate and invertebrate glia to prevent light-induced retinal degeneration and provide structural and physiological support for photoreceptors

Summary

Introduction

Glia have been recognized as a major and heterogeneous non-neuronal cell type in the nervous system for more than 150 years, but their chief homeostatic and regulatory roles in nervous system development and maintenance have only recently emerged [1,2,3,4]. One of the first described glial subtypes was Muller glia This specialized glial type is a radially-shaped macroglia that provides structural support, neuroprotection, and homeostatic recycling of energy, ions, and neurotransmitters for retinal neurons, some of the most active neurons in the body [5,6,7]. In some vertebrates (e.g. zebrafish and embryonic chick), Muller glia can serve as a source of stem cells for retinal regeneration [10], much like radial glia in other parts of the developing nervous system [11,12]. This suggests the presence of overlapping developmental and functional “networks” among different glial subtypes

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