Zhang H, Miller R H
Department of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
J Neurosci. 1996 Nov 1;16(21):6886-95. doi: 10.1523/JNEUROSCI.16-21-06886.1996.
The myelin sheath in the vertebrate CNS is formed by oligodendrocytes. The number of oligodendrocytes in a mature axon tract must be sufficient to myelinate all appropriate axons. How the number of oligodendrocytes is matched to axonal requirements and whether such matching involves axon-oligodendrocyte signaling or intrinsic oligodendrocyte self-regulation are not clear. Using a combination of in vitro analyses, we demonstrate that oligodendrocyte precursors closely regulate their numbers through interactions between adjacent precursors. In low-density rat spinal cord cultures, the number of oligodendrocyte lineage cells increases rapidly. The addition of large numbers of oligodendrocyte precursors substantially reduces precursor expansion and results in a normalization of oligodendrocyte lineage cell numbers in the cultures over time. Thus, the number of oligodendrocyte lineage cells that develop appears dependent on the density of oligodendrocyte lineage cells. This normalization of cell number is reflected in assays of clonal potential and proliferation. For example, precursors gave rise to fewer progeny and proliferated less at high density. Reduced precursor expansion at high density was not attributable to the depletion of growth factors. Cocultures of high and low densities did not inhibit precursor expansion in low-density cultures, suggesting the requirement for local cell-cell interactions. The inhibition of precursor expansion was cell-type-specific and dependent on the presence of oligodendrocyte lineage cells. We propose that this density-dependent feedback inhibition of oligodendrocyte precursor expansion may play a primary role in regulating the number of oligodendrocytes in the developing spinal cord.
脊椎动物中枢神经系统中的髓鞘由少突胶质细胞形成。成熟轴突束中的少突胶质细胞数量必须足以使所有合适的轴突形成髓鞘。少突胶质细胞的数量如何与轴突需求相匹配，以及这种匹配是否涉及轴突 - 少突胶质细胞信号传导或少突胶质细胞内在的自我调节尚不清楚。通过结合体外分析，我们证明少突胶质细胞前体通过相邻前体之间的相互作用密切调节其数量。在低密度大鼠脊髓培养物中，少突胶质细胞谱系细胞的数量迅速增加。添加大量少突胶质细胞前体可显著减少前体的扩增，并导致培养物中少突胶质细胞谱系细胞数量随时间恢复正常。因此，发育的少突胶质细胞谱系细胞数量似乎取决于少突胶质细胞谱系细胞的密度。这种细胞数量的正常化反映在克隆潜力和增殖测定中。例如，在高密度下，前体产生的后代较少且增殖较少。高密度下前体扩增减少并非由于生长因子的耗尽。高密度和低密度共培养不会抑制低密度培养物中前体的扩增，这表明需要局部细胞 - 细胞相互作用。前体扩增的抑制是细胞类型特异性的，并且依赖于少突胶质细胞谱系细胞的存在。我们提出，这种少突胶质细胞前体扩增的密度依赖性反馈抑制可能在调节发育中的脊髓中少突胶质细胞的数量方面起主要作用。
