Glial Cells in Neural Development


Glial cells and neurons depend on each other from birth to death. Glial cells accomplish many tasks for the proper development of the nervous system and for the maintenance of neurological functions. This review focuses on recent findings in the simple Drosophila model and underlines the similarities and differences between fly and vertebrate glia. The molecular and cellular mechanisms underlying gliogenesis will be reviewed as well as the role of the master regulatory gene of the glial fate: glial cells deficient/glial cells missing (glide/gcm). All along the review, the features shared between glia and macrophages are highlighted, as glide/gcm is also required in macrophage development and fly glia behave as nervous system‐specific scavenger cells. Finally, the recent data about the developmental pathways and the role of fly glia prompt us to reconsider the origin of glial cells during evolution.

Key Concepts:

  • Glial cells are very diversified in terms of morphology, function and gene expression profile.

  • Glial cells are absolutely required for nervous system development and to support neuronal functions.

  • Vertebrate and invertebrate nervous systems share many similarities.

  • Glial cells are the immune cells of the Drosophila nervous system.

  • Glial cells are very dynamic and migrate collectively over long distances.

  • Most glia and neurons arise from common precursors.

  • glide/gcm transcription factor represents the master gene of the glial fate in Drosophila acting as a genetic switch between neuron and glia.

  • glide/gcm is expressed and required in Drosophila glia and macrophages.

  • Glia and macrophages share molecular and cellular pathways.

  • The gcm ortholog genes are not necessary in vertebrate glial development.

Keywords: gliogenesis; glide/gcm; hemocytes; Drosophila; nervous system development; stem cells; microglia; immune system; evolution; blood–brain barrier

Figure 1.

Lateral glial cell subtypes in the embryonic ventral nerve cord (VNC). In the CNS, lateral glial cell subtypes are defined according to their position (surface, neuropile and cortex). A VNC transversal section from a mature embryo is represented. Glial cells associated with the cortex (in red) are called cell body glia (CBG). They are in contact with neuronal cell bodies. Among glial cells associated with axons (in green), longitudinal glia (LG) are located on the neuropile surface whereas nerve root glia (NRG) ensheath the peripheral nerves that exit the VNC. Among the cells present on the VNC surface (in blue), subperineural glia (SPG) are located on the outer surface whereas channel glia (CG) are positioned along the dorsoventral channel between the hemineuromeres. (Adapted from Beckervordersandforth et al., . Copyright by Elsevier.)

Figure 2.

Schematic representation of a Drosophila developing wing. Glia (in red) and neurons originate from sensory organ precusors. In the Drosophila deloping wing, two vein, L1 and L3, are inervated. Only three sensory organs are gliogenic on the L3 vein (asterisk). Neurons send their axons (in blue) before the start of glial migration. Glia move as a chain along the axon bundles. They migrate proximally from their place of birth toward the CNS. After completion of migration, glia form a continous sheath around the axon bundles. Along the L1 nerve, pioneer glia, at the tip of the chain, are identified to promote migration efficiency.

Figure 3.

Glia originate from different precursors. In the embryonic CNS, two kinds of neuroglioblasts (NGBs) delaminate from the neurogenic epithelium. Type 1 NGBs divide once asymmetrically to produce one neuroblast and one glioblast, which then proliferate to produce respectively neurons and glia. In Type 2 NGBs, ganglion mother cells (GMCs) first produce only neurons. After several divisions, mixed GMCs are generated and produce both neurons and glia. In the adult PNS, neurons and glia arise from glia sensory organ precursors (SOP). The SOP divides several times to produce PIIa, PIIb, PIIIb precursors and the gliogenic precursor GP1. The GP1 gives rise to a variable number of glia. PIIa generates the tormogen (To) and the trichogen (Tr), the accessory cells of the sensory organ, whereas PIIb generates the neuron (N) and the sheath cell (Sh). Blue and red colours indicate a neurogenic and gliogenic potential, respectively. (Adapted from Soustelle and Giangrande, . Copyright by Cambridge University Press.)

Figure 4.

The asymmetric division of the neuroglioblast (NGB). Representation of an asymmetrically dividing type 1 NGB. To generate a glioblast (GB), gcmmRNA is asymmetrically distributed at metaphase. The daughter cell that inherits high amounts of gcmmRNA triggers the expression of genes promoting glial fate such as repo and becomes a GB; The GB then divides and produces glial cells. The daughter cell receiving less gcmmRNA becomes a neuroblast (NB). The neuroblast then divides and produces only neurons.

Figure 5.

gcm act as a molecular switch between neurons and glia. In wild type neural stem cells (NSCs), gcm is expressed to promote the glial fate. Mixed neuroglioblasts (NGB) produce both neurons and glia. In gcm deficient animals (gcm Loss‐of‐function or LOF), glia are converted into neurons. Accordingly, gcm ectopic expression in NSCs (gcmGain‐of‐function or GOF) leads to extopic gliogenesis at the expense of neuronal differentiation. (Adapted from Soustelle and Giangrande and Jones BW . Copyright by Cambridge University Press/Elsevier.)



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Trébuchet, Guillaume, and Giangrande, Angela(Aug 2012) Glial Cells in Neural Development. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023740]