Oligodendrocyte Progenitor Marker Research Articles

Monoclonal antibody 14F7, which recognizes a stage-specific immature oligodendrocyte surface molecule, inhibits oligodendrocyte differentiation mediated in co-culture with astrocytes.

Cells at an intermediate stage of oligodendrocyte lineage are not only well characterized by biochemical studies but also are likely to relate to the outcome of physiological events. To elucidate the molecular events leading to the development of oligodendrocyte lineage cells, we have raised monoclonal antibodies against stage-specific immature oligodendrocytes, which have previously been isolated by a novel oligodendrocyte-lineage cell culture technique (Sakurai et al.: J Neurosci Res 52:17-26, 1998). We have isolated a mouse monoclonal antibody termed 14F7 which predominantly labels stage-specific immature oligodendrocytes and have found that the expression of 14F7 immunoreactivity in the developing neonatal rat forebrain is closely associated with cells expressing the oligodendrocyte progenitor marker A2B5 and to immature oligodendrocyte expressing O4 antigen. 14F7+ cells were distributed in the ventricular and subventricular zone and the nearby forming corpus callosum as non-myelinating cells. In contrast to cell culture observations, 14F7+ cells were seen only in oligodendrocyte lineage cells. For instance, dissociated cell culture studies indicated that 14F7 labels a cell surface molecule, and its cellular distribution is coincident with all of O4+ cells and A2B5+ cells, and even A2B5- cells. By contrast, 14F7-positive cells did not label astrocytes and, furthermore, did not label myelin basic protein (MBP)-positive oligodendrocytes. 14F7 recognized a 48-kDa protein on sodium dodecyl sulfate polyacrylamide gel electrophoresis. 14F7 immunoreactivity was detectable in rat brain as early as embryonic day 18. Furthermore, in these cells, the total time for differentiation was extended, and on maturation, these cells subsequently expressed an array of myelin-specific proteins, which normally occurs by direct contact with type-1 astrocytes. However, in the presence of 14F7, stage-specific oligodendrocytes co-cultured with astrocytes completely failed to express MBP. These data suggest that the 14F7 antigen is a novel cell surface molecule that is expressed in the intermediate stage of oligodendrocyte-lineage cells, and it is expected that it regulates the differentiation of oligodendrocyte throughout development.

Monoclonal antibody 14F7, which recognizes a stage‐specific immature oligodendrocyte surface molecule, inhibits oligodendrocyte differentiation mediated in co‐culture with astrocytes

Cells at an intermediate stage of oligodendrocyte lineage are not only well characterized by biochemical studies but also are likely to relate to the outcome of physiological events. To elucidate the molecular events leading to the development of oligodendrocyte lineage cells, we have raised monoclonal antibodies against stage-specific immature oligodendrocytes, which have previously been isolated by a novel oligodendrocyte-lineage cell culture technique (Sakurai et al.: J Neurosci Res 52:17–26, 1998). We have isolated a mouse monoclonal antibody termed 14F7 which predominantly labels stage-specific immature oligodendrocytes and have found that the expression of 14F7 immunoreactivity in the developing neonatal rat forebrain is closely associated with cells expressing the oligodendrocyte progenitor marker A2B5 and to immature oligodendrocyte expressing O4 antigen. 14F7+ cells were distributed in the ventricular and subventricular zone and the nearby forming corpus callosum as non-myelinating cells. In contrast to cell culture observations, 14F7+ cells were seen only in oligodendrocyte lineage cells. For instance, dissociated cell culture studies indicated that 14F7 labels a cell surface molecule, and its cellular distribution is coincident with all of O4+ cells and A2B5+ cells, and even A2B5− cells. By contrast, 14F7-positive cells did not label astrocytes and, furthermore, did not label myelin basic protein (MBP)-positive oligodendrocytes. 14F7 recognized a 48-kDa protein on sodium dodecyl sulfate polyacrylamide gel electrophoresis. 14F7 immunoreactivity was detectable in rat brain as early as embryonic day 18. Furthermore, in these cells, the total time for differentiation was extended, and on maturation, these cells subsequently expressed an array of myelin-specific proteins, which normally occurs by direct contact with type-1 astrocytes. However, in the presence of 14F7, stage-specific oligodendrocytes co-cultured with astrocytes completely failed to express MBP. These data suggest that the 14F7 antigen is a novel cell surface molecule that is expressed in the intermediate stage of oligodendrocyte-lineage cells, and it is expected that it regulates the differentiation of oligodendrocyte throughout development. J. Neurosci. Res. 54:79–96, 1998. © 1998 Wiley-Liss, Inc.

Oligodendrocyte progenitors are generated throughout the embryonic mouse brain, but differentiate in restricted foci.

Recent evidence from studies mapping the expression of putative oligodendrocyte progenitor specific mRNAs has suggested that oligodendrocyte progenitors arise during embryogenesis, in specific foci of the neuroectoderm. In order to test this hypothesis, we have assayed different regions of the embryonic central nervous system for their ability to generate oligodendrocytes following transplantation into neonatal cerebrum. To allow identification of donor-derived oligodendrocytes in wild-type host brain, we used the MbetaP transgenic mouse, which expresses lacZ in oligodendrocytes, as donor tissue. We found that tissue fragments derived from several levels of the anterior-posterior axis of the neural tube at E14.5 and E12.5, chosen to include (hindbrain, cervical and lumbar spinal cord), or exclude (dorsal telencephalon) putative foci of oligodendrocyte progenitors, all produced oligodendrocytes following transplantation. In addition, these same regions taken from E10.5, prior to the appearance of putative oligodendrocyte progenitor markers, also all yielded oligodendrocytes on transplantation. This indicates that precursor cells that can generate oligodendrocytes are widespread throughout the neuroectoderm as early as E10.5. We have also used the oligodendrocyte lineage-specific glycolipid antibodies O4, R-mAb and O1 to identify those regions of the developing brain that first support the differentiation of oligodendrocytes from their progenitor cells. We found that the first oligodendrocytes arise in prenatal brain at E14.5, in a restricted zone adjacent to the midline of the medulla. These cells are mitotically inactive, differentiated oligodendrocytes and, using light and electron microscopy, we show that they become functional, myelin-bearing oligodendrocytes. We have mapped the subsequent appearance of differentiated oligodendrocytes in the prenatal brain and show that they appear in a restricted, tract-specific manner. Our results suggest that oligodendrocytes are generated from neuroectodermal cells positioned throughout the rostrocaudal axis of the neural tube, rather than at restricted locations of the neuroectoderm. By contrast, the differentiation of such cells into oligodendrocytes does occur in a restricted manner, consistent with local regulation of oligodendrocyte progenitor differentiation.