Wada T, Kagawa T, Ivanova A, Zalc B, Shirasaki R, Murakami F, Iemura S, Ueno N, Ikenaka K
Laboratory of Neural Information, National Institute for Physiological Sciences, 38 Nishigonaka, Myodaiji, Okazaki, 444-8585, Japan.
Dev Biol. 2000 Nov 1;227(1):42-55. doi: 10.1006/dbio.2000.9869.
Oligodendrocytes are the myelinating cells of the mammalian central nervous system. In the mouse spinal cord, oligodendrocytes are generated from strictly restricted regions of the ventral ventricular zone. To investigate how they originate from these specific regions, we used an explant culture system of the E12 mouse cervical spinal cord and hindbrain. In this culture system O4(+) cells were first detected along the ventral midline of the explant and were subsequently expanded to the dorsal region similar to in vivo. When we cultured the ventral and dorsal spinal cords separately, a robust increase in the number of O4(+) cells was observed in the ventral fragment. The number of both progenitor cells and mature cells also increased in the ventral fragment. This phenomenon suggests the presence of inhibitory factor for oligodendrocyte development from dorsal spinal cord. BMP4, a strong candidate for this factor that is secreted from the dorsal spinal cord, did not affect oligodendrocyte development. Previous studies demonstrated that signals from the notochord and ventral spinal cord, such as sonic hedgehog and neuregulin, promote the ventral region-specific development of oligodendrocytes. Our present study demonstrates that the dorsal spinal cord negatively regulates oligodendrocyte development.
少突胶质细胞是哺乳动物中枢神经系统的髓鞘形成细胞。在小鼠脊髓中，少突胶质细胞由腹侧脑室区严格受限的区域产生。为了研究它们如何起源于这些特定区域，我们使用了E12小鼠颈脊髓和后脑的外植体培养系统。在这个培养系统中，首先沿着外植体的腹侧中线检测到O4(+)细胞，随后它们向背侧区域扩展，类似于在体内的情况。当我们分别培养腹侧和背侧脊髓时，在腹侧片段中观察到O4(+)细胞数量显著增加。腹侧片段中祖细胞和成熟细胞的数量也增加了。这种现象表明存在抑制背侧脊髓少突胶质细胞发育的因子。骨形态发生蛋白4（BMP4）是这种因子的一个强有力候选者，它由背侧脊髓分泌，但不影响少突胶质细胞的发育。先前的研究表明，来自脊索和腹侧脊髓的信号，如音猬因子和神经调节蛋白，促进少突胶质细胞腹侧区域特异性发育。我们目前的研究表明，背侧脊髓对少突胶质细胞发育起负调节作用。
