Glial plasticity at nervous system transition zones

Abstract

The central and peripheral nervous systems (CNS and PNS, respectively) are two separate yet connected domains characterized by molecularly distinct cellular components that communicate via specialized structures called transition zones to allow information to travel from the CNS to the periphery, and vice versa. Until recently, nervous system transition zones were thought to be selectively permeable only to axons, and the establishment of the territories occupied by glial cells at these complex regions remained poorly described and not well understood. Recent work now demonstrates that transition zones are occupied by dynamic glial cells and are precisely regulated over the course of nervous system development. This review highlights recent work on glial cell migration in and out of the spinal cord, at motor exit point (MEP) and dorsal root entry zone (DREZ) transition zones, in the physiological and diseased nervous systems. These cells include myelinating glia (oligodendrocyte lineage cells, Schwann cells and motor exit point glia), exit glia, perineurial cells that form the perineurium along spinal nerves, as well as professional and non-professional phagocytes (microglia and neural crest cells).

Keywords: Dorsal root entry zone; Glia; Migration; Motor exit point; Nervous system; Transition zone.

Fig. 1.

A subset of oligodendrocyte lineage cells interacts with the developing dorsal root entry zone. Oligodendrocyte lineage cells (OLC, green) contact pioneering sensory axons (magenta) as they enter the spinal cord at the dorsal root entry zone (DREZ). Upon contact, these OLCs adopt a sensory oligodendrocyte (sOLC) identity.

Fig. 2.

Microglia exit the CNS in a model of spinal root avulsion. (A) Diagram of a cross section of the spinal cord showing the intact peripheral and central branches of the dorsal rot ganglion (DRG) at a control DREZ, and an injured central branch at an avulsed DREZ. (B) Nitrogen-pulsed laser axotomy of the central branch of the DRG mimics spinal root avulsion. (C) Microglia are found exclusively inside the CNS (0) at the control DREZ. In the avulsed DREZ, microglia are observed exiting the spinal cord and phagocytose cell debris in the PNS (1). Almost half of these emigrated microglia return to the CNS over the next 24 h, carrying peripheral debris engulfed in their cytoplasm (2).

Fig. 3.

Boundary cells restrict CNS components to the spinal cord at motor exit points. (A) In zebrafish, motor exit point (MEP) glia (light purple) restrict oligodendrocyte lineage cells (OLC, green) to the spinal cord at control MEP transition zones (TZ). Upon genetic or laser ablation of MEP glia, OLCs migrate onto spinal motor nerves in the PNS. (B) In mouse, boundary cap cells (BC cells, orange) constrain CNS components to the spinal cord at MEP transition zones. In the absence of BC cells, central nervous system glia and motor neurons are found in the PNS.

Fig. 4.

Phagocytic neural crest cells enter the spinal cord through motor exit point transition zones during early development. Neural crest cells (blue) migrate along the zebrafish neural tube and phagocytose PNS debris (magenta) until 36 h post fertilization. These non-professional phagocytes are occasionally found entering the spinal cord through motor exit point (MEP) transition zones and engulf debris in the CNS.