The glia of Caenorhabditis elegans

Abstract

Glia have been, in many ways, the proverbial elephant in the room. Although glia are as numerous as neurons in vertebrate nervous systems, technical and other concerns had left research on these cells languishing, whereas research on neurons marched on. Importantly, model systems to study glia had lagged considerably behind. A concerted effort in recent years to develop the canonical invertebrate model animals, Drosophila melanogaster and Caenorhabditis elegans, as settings to understand glial roles in nervous system development and function has begun to bear fruit. In this review, we summarize our current understanding of glia and their roles in the nervous system of the nematode C. elegans. The recent studies we describe highlight the similarities and differences between C. elegans and vertebrate glia, and focus on novel insights that are likely to have general relevance to all nervous systems.

Figure 1

The amphid sensory organ is a model system for neuron-glia interactions. A: Schematic of an adult C. elegans hermaphrodite. The amphids are located in the head. B: Each amphid consists of twelve neurons (in green; only one is drawn here for simplicity) and two glial cells, the sheath (AMsh, in red) and the socket (in blue). C: Processes from the neurons and glia come together at the tip of the nose. The glial cells align to form a tube, the amphid channel, through which some amphid neuron dendrites extend sensory cilia that adopt distinct morphologies: single cilia (neurons ASE, ASG, ASH, ASI, ASJ, ASK), double cilia (neurons ADF, ADL), wing cilia (neurons AWA, AWB, AWC) and the finger cilia of AFD. Adherens junctions between the dendrites and the sheath glia, as well as between the sheath and socket glia establish a niche for the sensory cilia. This niche is filled with matrix material secreted by the sheath glia; thus, the site where the nervous system of the animal meets the environment is under the direct control of glia. Adapted from Perkins et al., 1986.

Figure 2

The cephalic sheath glia (CEPsh glia) physically interact with both the sensory receptive endings of the CEP neurons, and with the nerve ring. A: The CEP sensillum displays the same basic architecture as the amphid. A thin anterior process from the CEPsh glia runs parallel to the CEP neuron, while a sheet-like posterior process wraps around the “brain” of the animal. B: The anterior process establishes a channel similar to, but smaller than the amphid channel. C: Thin projections from the posterior process enter the nerve ring and can ensheath synapses, similar to astrocytes of vertebrate systems. Adapted from White et al., 1986. D: Schematic of a cross-section through the nerve ring. Each animal has four CEPsh glia that wrap around the nerve ring without overlapping with each other. Thus, CEPsh glia establish independent domains, in a fashion reminiscent of astrocytic domains.

Figure 3

The GLR glia establish gap junctions that bridge neurons with muscles. A: Each animal has six GLR glia. Only one is depicted here. The cell body lies posterior to the nerve ring. An anterior, sheet-like process lines the inside of the nerve ring and then tapers to a thinner process. B: The sheet-like processes of the GLR glia make gap junctions to head muscle cells and the RME motor neurons that innervate them. Adapted from White et al., 1986.

Figure 4

The size of the amphid glia channel is regulated by two opposing forces. DAF-6/Patched-related acts within the glia to reduce channel girth, while CHE-14/Dispatched and the LIT-1/Nemo-like kinase MAPK module act (also within glia) to increase channel cross-section. Unidentified neuronal signals are required for the correct localization of DAF-6 and LIT-1, as well as normal channel morphogenesis.

Figure 5

Embryonic ablation of glia results in dendrite extension and axonal guidance defects. A: Ablation of the amphid sheath glia during embryogenesis results in amphid neurons with dendrites that are much shorter than normal, reminiscent of dex-1 and dyf-7 mutants (see text). B: Ablation of the CEPsh glia results in slightly shorter CEP dendrites, and axon guidance defects.

Figure 6

Ablation of the amphid sheath glia in adult animals can result in severe disruption of the morphology of neuronal receptive endings. Left panel, unablated amphid. Glia, green; AWC neuron, red. Right panel, glia-ablated amphid. Note loss of extended sensory receptive ending of AWC neuron. Scale bar 5μm. Adapted from Bacaj et al., 2008.

Figure 7

Glia are required for sensory receptive ending remodeling. A: Diagram of a cross-section at the tip of the head. The wing-like processes of the bilateral AWC neurons are ensheathed by the bilateral amphid sheath glia (L and R for left and right respectively). B: In dauer animals the glia expand and fuse to accommodate the expansion of the neuronal wing processes. C: If glia lack ttx-1 they fail to expand and fuse, resulting in lack of neuronal remodeling. D: Conversely, glia remodeling takes place independently of neurons.

Figure 8

Neuronal development in vertebrates and C. elegans. In vertebrates, neurons are born in excess and then undergo a selection process that is hypothesized to include competition for glia-derived survival factors. In C. elegans, neurons, like all cells of the soma, are born in a predetermined fashion, and in predetermined numbers. Their survival does not depend on signals from other cells, including glia. Therefore, in contrast to vertebrates, C. elegans glia can be ablated without neuronal demise, and the role of glia in neuronal function can be probed in vivo.