Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents.

Carl Trolle,Svitlana Vasylovska,Elena N Kozlova,Niclas Konig,Ninnie Abrahamsson

doi:10.1186/1471-2202-15-60

Carl Trolle, Svitlana Vasylovska + Show 3 more

Open Access

https://doi.org/10.1186/1471-2202-15-60

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Journal: BMC neuroscience	Publication Date: May 5, 2014
Citations: 51	License type: cc-by

Affiliation: Uppsala University

Abstract

BackgroundThe boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse boundary cap neural crest stem cells (bNCSCs) implanted to the injured DRTZ after dorsal root avulsion for their potential to assist sensory axon regeneration.ResultsGrafted cells showed extensive survival and differentiation after transplantation to the avulsed DRTZ. Transplanted cells located outside the spinal cord organized elongated tubes of Sox2/GFAP expressing cells closely associated with regenerating sensory axons or appeared as small clusters on the surface of the spinal cord. Other cells, migrating into the host spinal cord as single cells, differentiated to spinal cord neurons with different neurotransmitter characteristics, extensive fiber organization, and in some cases surrounded by glutamatergic terminal-like profiles.ConclusionsThese findings demonstrate that bNCSCs implanted at the site of dorsal root avulsion injury display remarkable differentiation plasticity inside the spinal cord and in the peripheral compartment where they organize tubes associated with regenerating sensory fibers. These properties offer a basis for exploring the ability of bNCSCs to assist regeneration of sensory axons into the spinal cord and replace lost neurons in the injured spinal cord.

Highlights

The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development
Migration of boundary cap neural crest stem cells (bNCSCs) into the spinal cord is likely to be the result of the combined production and release of growth/migration supporting factors by cells in the peripheral [18], and central nervous system that respond to the degenerative processes in the spinal cord [19] or at the DRTZ [20]
We noted striking differences in the differentiation of bNCSCs located in the peripheral nervous system (PNS) outside the spinal cord compared to cells, which had migrated into the spinal cord

Summary

Introduction

The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Boundary cap neural crest stem cells (bNCSCs) are neural crest derivatives that populate the entry/exit points of spinal roots during embryonic development [1] They appear to participate in regulating growth of sensory axons into the spinal cord [2], and prevent spinal motor neurons [3] and central neuroglial cells [4] to enter the peripheral nervous system (PNS) [2,5,6]. Since boundary cap cells are part of the growth permissive environment at the dorsal root-spinal cord junction during development we tested whether bNCSCs placed to their native position can assist sensory axon regeneration after dorsal root avulsion injury [11]

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