Park Hae-Chul, Shin Jimann, Appel Bruce
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Development. 2004 Dec;131(23):5959-69. doi: 10.1242/dev.01456.
Graded Hedgehog (Hh) signaling patterns the spinal cord dorsoventral axis by inducing and positioning distinct precursor domains, each of which gives rise to a different type of neuron. These domains also generate glial cells, but the full range of cell types that any one precursor population produces and the mechanisms that diversify cell fate are unknown. By fate mapping and clonal analysis in zebrafish, we show that individual ventral precursor cells that express olig2 can form motoneurons, interneurons and oligodendrocytes. However, olig2+ precursors are not developmentally equivalent, but instead produce subsets of progeny cells in a spatially and temporally biased manner. Using genetic and pharmacological manipulations, we provide evidence that these biases emerge from Hh acting over time to set, maintain, subdivide and enlarge the olig2+ precursor domain and subsequently specify oligodendrocyte development. Our studies show that spatial and temporal differences in Hh signaling within a common population of neural precursors can contribute to cell fate diversification.
分级的刺猬（Hh）信号通过诱导和定位不同的前体结构域来塑造脊髓的背腹轴，每个前体结构域都会产生不同类型的神经元。这些结构域也会产生神经胶质细胞，但任何一个前体细胞群体产生的细胞类型的完整范围以及使细胞命运多样化的机制尚不清楚。通过在斑马鱼中进行命运图谱和克隆分析，我们发现表达olig2的单个腹侧前体细胞可以形成运动神经元、中间神经元和少突胶质细胞。然而，olig2 +前体在发育上并不等同，而是以空间和时间偏向的方式产生子代细胞的亚群。通过基因和药理学操作，我们提供证据表明，这些偏向源于Hh随着时间的推移发挥作用，以设定、维持、细分和扩大olig2 +前体结构域，随后确定少突胶质细胞的发育。我们的研究表明，在共同的神经前体细胞群体中，Hh信号的空间和时间差异可有助于细胞命运的多样化。
