Vartanian T, Fischbach G, Miller R
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):731-5. doi: 10.1073/pnas.96.2.731.
Oligodendrocytes develop from a subpopulation of precursor cells within the ventral ventricular zone of the spinal cord. The molecular cues that direct this spatially and temporally restricted event seem to originate in part from structures ventral to and within the spinal cord. Here, we present evidence that the family of ligands termed neuregulins are necessary for the normal generation of mouse spinal cord oligodendrocytes. Oligodendrocytes mature in spinal cord explants from wild-type mice and mice heterozygotic for a null mutation in the neuregulin gene (NRG +/-) in a temporal sequence of developmental events that replicates that observed in vivo. However, in spinal cord explants derived from mice lacking neuregulin (NRG -/-), oligodendrocytes fail to develop. Addition of recombinant neuregulin to spinal cord explants from NRG -/- mice rescues oligodendrocyte development. In wild-type spinal cord explants, inhibitors of neuregulin mimic the inhibition of oligodendrocyte development that occurs in NRG -/- explants. In embryonic mouse spinal cord, neuregulins are present in motor neurons and the ventral ventricular zone where they likely exert their influence on early oligodendrocyte precursor cells.
少突胶质细胞由脊髓腹侧脑室区的一群前体细胞发育而来。指导这一在空间和时间上受限事件的分子信号似乎部分源自脊髓腹侧及脊髓内部的结构。在此，我们提供证据表明，被称为神经调节蛋白的配体家族对于小鼠脊髓少突胶质细胞的正常生成是必需的。少突胶质细胞在来自野生型小鼠和神经调节蛋白基因无效突变杂合子小鼠（NRG+/-）的脊髓外植体中，按照与体内观察到的发育事件时间顺序相同的方式成熟。然而，在来自缺乏神经调节蛋白的小鼠（NRG-/-）的脊髓外植体中，少突胶质细胞无法发育。向来自NRG-/-小鼠的脊髓外植体中添加重组神经调节蛋白可挽救少突胶质细胞的发育。在野生型脊髓外植体中，神经调节蛋白抑制剂模拟了NRG-/-外植体中发生的少突胶质细胞发育抑制。在胚胎小鼠脊髓中，神经调节蛋白存在于运动神经元和腹侧脑室区，它们可能在这些区域对早期少突胶质前体细胞发挥作用。
