Abstract

Tiling is a developmental process where cell populations become evenly distributed throughout a tissue. In this review, we discuss the developmental cellular tiling behaviors of the two major glial populations in the central nervous system (CNS)—oligodendrocyte progenitor cells (OPCs) and astrocytes. First, we discuss OPC tiling in the spinal cord, which is comprised of the three cellular behaviors of migration, proliferation, and contact-mediated repulsion (CMR). These cellular behaviors occur simultaneously during OPC development and converge to produce the emergent behavior of tiling which results in OPCs being evenly dispersed and occupying non-overlapping domains throughout the CNS. We next discuss astrocyte tiling in the cortex and hippocampus, where astrocytes migrate, proliferate, then ultimately determine their exclusive domains by gradual removal of overlap rather than sustained CMR. This results in domains that slightly overlap, allowing for both exclusive control of “synaptic islands” and astrocyte-astrocyte communication. We finally discuss the similarities and differences in the tiling behaviors of these glial populations and what remains unknown regarding glial tiling and how perturbations to this process may impact injury and disease.

Highlights

  • Tiling is a cellular behavior during development where, following specification, a population of cells migrate and become evenly dispersed, forming non-overlapping domains with their neighbors

  • Glial tiling is routinely described in the literature, there has been little investigation into the molecular mechanisms that contribute to the various cellular processes that drive this process (Bushong et al, 2002, 2004; Halassa et al, 2007; Hughes et al, 2013; De Biase et al, 2017)

  • Utilizing both CRISPR/Cas9-mediated met mutagenesis and dominant negative Met transgenic fish, we demonstrated that loss of Met signaling significantly reduced the number of migrating oligodendrocyte progenitor cells (OPCs) during developmental tiling

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Summary

INTRODUCTION

OPCs are not the only glial population that exhibits tiling behavior. Astrocytes, which make up between 20 and 40% of the total brain cell count (Khakh and Sofroniew, 2015), cover the entire CNS with minimal overlap (Bushong et al, 2002). Protoplasmic astrocytes, in particular, occupy distinct individual areas with little overlap despite their extensive branching (Bushong et al, 2004), a phenomenon similar to the tiling behavior seen in OPCs and neurons. We refer to these areas controlled by a single astrocyte as ‘‘domains’’ or ‘‘territories’’. Astrocytes typically do not have significant overlap with their neighbors, other glial cell types are able to freely infiltrate their territories and form overlapping domains, demonstrating that tiling is controlled differently when considering homo vs heterotypic interactions (Bushong et al, 2002) This is even true for different astrocyte subtypes. It follows that more emphasis may be placed on tiling and astrocyte networks in the future

Findings
CONCLUDING REMARKS

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