Identity and lineage fate of proteolipid protein 1 gene (Plp1)-expressing cells in the embryonic murine spinal cord

Abstract

Background: The proteolipid protein (PLP) is the most abundant protein in the myelin sheath of the central nervous system (CNS). The gene coding PLP, proteolipid protein 1 (Plp1) is highly expressed in oligodendrocytes, the myelin-forming cells in the CNS. Previous studies demonstrate that Plp1 gene is expressed in the embryonic CNS much earlier before the generation of oligodendrocytes. However, the progenitor identity and the fate of Plp1-expressing cells are still elusive.

Results: We employed genetic approaches to permanently label Plp1-expressing cells with the reporter enhanced yellow fluorescence protein (EYFP) and used multicolored immunohistochemistry to characterize their identity and lineage fate. We found that Plp1-expressing cells were initially present without spatial restrictions and later confined to the ventral progenitor domains of the embryonic spinal cord. Our fate-mapping results showed that Plp1-expressing cells during early embryogenesis were multipotent neural progenitor cells that gave rise to not only neurons but also glial progenitor cells whereas they were bipotent glial progenitor cells during later neural development stages and generated oligodendroglial and astroglial lineage cells but not neurons. Intriguingly, postnatal astrocytes generated from embryonic Plp1-expressing glial progenitor cells were present only in the ventral spinal cord.

Conclusion: Our study reveals that Plp1-expressing cells during embryonic neural development display dynamic cellular identities and have a broader lineage fate than oligodendroglial lineage.

Keywords: Cre-loxP; PLP/DM20; embryonic neural stem cells; fate mapping; genetic labeling; myelination; neural progenitor cells; oligodendrocytes; proteolipid protein.