The many glia of a tiny nematode: studying glial diversity using Caenorhabditis elegans

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Karolina Mizeracka, Maxwell G. Heiman

Published Online: Jan 21 2015

DOI: 10.1002/wdev.171

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ABSTRACT Glia constitute a major, understudied population of cells in the nervous system. Currently, it is appreciated that these cells exhibit vast morphological, functional, and molecular diversity, but our understanding of glial biology is limited. Some key unanswered questions include how glial diversity is generated during development and what functions distinct glial subtypes serve in the mature nervous system. The nematode Caenorhabditis elegans contains a defined set of glia, which have clear morphological and molecular differences, and thus provides a simplified model for understanding glial diversity. In addition, recent experiments suggest that the molecular mechanisms underlying the generation of glial diversity in C. elegans are conserved with those in mammals. In this review, we summarize the surprising diversity of glial subtypes present in this simple organism, and highlight current thinking about what roles they perform in the nervous system. We emphasize how genetic approaches may be used to identify the mechanistic origins of glial diversity, which is key to understanding how glia function in health and disease. WIREs Dev Biol 2015, 4:151–160. doi: 10.1002/wdev.171 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Invertebrate Organogenesis > Worms Nervous System Development > Worms

Caenorhabditis elegans sense organs consist of three major cell types. Schematic of a generalized sense organ, showing a sensory neuron (red), sheath glial cell (dark blue), and socket glial cell (light blue). An unbranched dendrite extends through a channel in the sheath and socket glia, such that the nonmotile sensory cilium at its tip is exposed to the external environment. Apical junctions (green) exist between the neuron and sheath glial cell; the sheath and socket glia; and the socket glial cell and hypodermis, or skin (gray). The socket cell channel is lined by cuticle that is continuous with the cuticle of the hypodermis.

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Glial development. Working model of glial subtype specification: cells in neural lineages express the nonconserved factor, lin‐26, to select a glial rather than neuronal fate. The CEP sheath glial subtype (green) is specified by the conserved transcription factors, mls‐2/Nkx and vab‐3/Pax, whose expression starts during embryogenesis. In turn, these factors activate expression of transcription factors, such as hlh‐17, an Olig2 ortholog, that may control aspects of mature CEP sheath glial morphology or function. Presumably, similar transcription factor hierarchies specify other glial subtypes (red, blue), but these factors remain to be identified.

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Subtypes of sheath and socket glia. Examples of glial diversity: the amphid sheath glial cell (AM, red), the cephalic sheath glial cell (CEP, green) and the lateral inner labial socket glial cell (IL, blue). The amphid sheath glial cell is larger than its counterparts in other sense organs and contains many matrix‐filled vesicles (inset). The CEP sheath glial cell has a bipolar morphology with a process that ensheathes the CEP neuron dendrite at the nose tip and a sheet‐like process that extends posteriorly to contact the nerve ring (arrow). CEP sheath glia have deep invaginations that form lamellae in the nerve channel (inset), a feature it shares with outer and inner labial (OL/IL) sheath glial cells (not pictured). The lateral IL socket glial cell is uniquely wrapped by an extension of the BAG neuron (inset).

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