Glial cell development and function in the Drosophila visual system

Abstract

In the developing nervous system, building a functional neuronal network relies on coordinating the formation, specification and survival to diverse neuronal and glial cell subtypes. The establishment of neuronal connections further depends on sequential neuron-neuron and neuron-glia interactions that regulate cell-migration patterns and axon guidance. The visual system of Drosophila has a highly regular, retinotopic organization into reiterated interconnected synaptic circuits. It is therefore an excellent invertebrate model to investigate basic cellular strategies and molecular determinants regulating the different developmental processes that lead to network formation. Studies in the visual system have provided important insights into the mechanisms by which photoreceptor axons connect with their synaptic partners within the optic lobe. In this review, we highlight that this system is also well suited for uncovering general principles that underlie glial cell biology. We describe the glial cell subtypes in the visual system and discuss recent findings about their development and migration. Finally, we outline the pivotal roles of glial cells in mediating neural circuit assembly, boundary formation, neural proliferation and survival, as well as synaptic function.

Keywords: Optic lobe; axon guidance; migration; neurogenesis; photoreceptor axons.

Fig. 1. Glial-cell subtypes and their roles in the larval and adult visual system

(A,B) Morphology of the 3rd instar larval visual system in frontal (A) and horizontal (B) orientations. R-cell axons (R1–R8) project from the eye imaginal disc through the optic stalk into the optic lobe. Retinal basal glial cells (RBGs) originate in the optic stalk and migrate into the eye disc. Progenitors in the outer proliferation center (OPC) closer to the lamina furrow (LF) give rise to lamina precursor cells (LPCs). These divide to generate lamina neurons (ln). Their cell bodies are organized into columns in close proximity with R-cell axons bundles. Satellite glial cells (sg) are positioned at the level of lamina neuron cell bodies. R1–R6 growth cones terminate between the rows of epithelial (eg) and marginal (mg) glial cells. These are born in glial precursor cell (GPC) areas and share a lineage with proximal medulla neurons (pmn). The arrowhead indicates the position of committed glial precursors adjacent to the R-cell projection field. Epithelial and marginal glial cells migrate to their characteristic positions above and below the lamina plexus. Proximally located progenitors in the OPC give rise to medulla neurons (mn). R7 and R8 axons stop in the medulla neuropil, which is delineated by medulla glial cells (meg) and medulla neuropil glial cells (mng). a, anterior; MF, morphogenetic furrow; p, posterior. (C,D) Morphology of the adult visual system. (C) In the lamina, R1–R6 axons and processes of lamina neurons L1–L5 are organized into cartridges. R7 and R8 axons innervate two neuropil layers (M3 and M6) in the medulla. (D) Schematic drawing of a lamina cartridge cross-section. Boxes in (B) and (D) indicate the developmental processes that are controlled by glial cells, as well as the genes that are associated with these functions.

Fig. 2. Glial cells in the adult visual system of Drosophila

R-cell axons are labeled in red using the R-cell specific marker mAb24B10. Glial nuclei (blue) and their processes (green) are labeled with the glial-specific marker Repo and by using repo-Gal4 to drive expression of membrane-bound green fluorescent protein (GFP), respectively. (A,A') R-cell axons project from the retina to the optic lobe comprising three ganglia, the lamina, medulla and lobula complex. R1–R6 axons stop in the lamina, whereas R7 and R8 axons terminate in the medulla. Different glial cell subtypes are found in each ganglion. Their processes extensively enwrap lamina cartridges and reflect the organization into layers and columns in the medulla. (B,B') High magnification of a cross-section through the lamina. Each lamina cartridge is enwrapped by glial cell processes (arrow). Glial-cell processes also surround individual R1–R6 terminals in each cartridge (arrowheads). (C,C') High magnification of distal medulla neuropil layers (boxes in A and A'). Glial-cell processes extend into medulla neuropil columns in the vicinity of R-cell axons (arrows).