Oligodendrocyte precursors originate at the ventral ventricular zone dorsal to the ventral midline region in the embryonic rat spinal cord

Abstract

The precursors for oligodendrocytes, the myelinating cells of the vertebrate CNS, appear to be initially restricted to ventral regions of the embryonic rat spinal cord. These cells subsequently populate dorsal spinal cord regions where they acquire the mature characteristics of oligodendrocytes. To determine the location and timing of proliferation of oligodendrocyte precursors in the ventral spinal cord, and to map their pathways of migration in vivo, an assay that identifies mitotic cells was used in conjunction with antibodies that distinguish astrocytes, oligodendrocytes and their precursors. Between E16.5 and E18.5, two hours after a maternal injection of BrdU, the majority of proliferating cells were located in a discrete cluster at the ventral ventricular zone dorsal to the ventral midline region of the developing spinal cord. By contrast, 12–24 hours following a BrdU injection at E16.5, increasing numbers of labeled cells were seen in the dorsal and more lateral locations of the spinal cord. These observations suggest that BrdU-labeled ventral ventricular cells, or their progeny migrate dorsally and laterally during subsequent spinal cord development. To determine the nature of these proliferating cells, cultures of dorsal and ventral spinal cord from BrdU-labeled animals were double-labeled with antibodies that identify oligodendrocytes or astrocytes and anti-BrdU. In dorsal spinal cord cultures derived from animals that had received a single injection of BrdU at E16.5, the majority of proliferating cells differentiated into astrocytes while, in ventrally derived cultures from the same animals, the majority of proliferating cells differentiated into oligodendrocytes. In dorsal cultures prepared from animals that received multiple injections of BrdU between E16.5 and E18.5, many more cells were labeled with BrdU and approximately half of these differentiated into oligodendrocytes. These observations suggest that during embryonic development proliferating oligodendrocyte precursors are initially located at the ventral ventricular zone dorsal to the ventral midline region of the spinal cord and during subsequent maturation these cells or their progeny migrated dorsally in the ventricular region of the spinal cord, and laterally to reside in the developing white matter.