FGF-dependent Notch signaling maintains the spinal cord stem zone
FGF-dependent Notch signaling maintains the spinal cord stem zone
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DOI：
10.1101/gad.357705
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发表时间：
2005-12-01
影响因子：
10.5
通讯作者：
Storey, KG
中科院分区：
文献类型：
--
作者：
Akai, J;Halley, PA;Storey, KG
脊髓的产生依赖于位于尾干区的未分化细胞的增殖。尽管成纤维细胞生长因子（FGF）信号是维持这一细胞群所必需的，但我们不知道它是如何在这种情况下控制细胞行为的。在这里，我们描述了Notch配体的一个被忽视的表达域，Delta1，在茎区，并证明这构成了一个增殖细胞群，其中Notch信号是活跃的。我们发现FGF信号是茎区前基因cash4表达所必需的，这反过来又诱导了Deltal。我们进一步证明Notch信号是干细胞区细胞增殖所必需的；然而，它不能调节细胞在该区域外的运动，Notch信号的缺失也不足以驱动该组织内的神经元分化。这些数据确定了Notch通路在脊椎动物神经发生过程中的新作用，其中高表达delta - 1的细胞之间的信号传导维持了产生脊髓的神经前体池。我们的研究结果还提示了细胞选择过程的建立机制，即侧抑制：当新形成的神经上皮中FGF活性下降时，表达Delta/ notch的干细胞之间的相互抑制转换为单个呈现Delta - 1的神经元。
Generation of the spinal cord relies on proliferation of undifferentiated cells located in a caudal stem zone. Although fibroblast growth factor (FGF) signaling is required to maintain this cell group, we do not know how it controls cell behavior in this context. Here we characterize an overlooked expression domain of the Notch ligand, Delta1, in the stem zone and demonstrate that this constitutes a proliferative cell group in which Notch signaling is active. We show that FGF signaling is required for expression of the proneural gene cash4 in the stem zone, which in turn induces Deltal. We further demonstrate that Notch signaling is required for cell proliferation within the stem zone; however, it does not regulate cell movement out of this region, nor is loss of Notch signaling sufficient to drive neuronal differentiation within this tissue. These data identify a novel role for the Notch pathway during vertebrate neurogenesis in which signaling between high Delta1-expressing cells maintains the neural precursor pool that generates the spinal cord. Our findings also suggest a mechanism for the establishment of the cell selection process, lateral inhibition: Mutual inhibition between Delta/Notch-expressing stem zone cells switches to single Delta1-presenting neurons as FGF activity declines in the newly formed neuroepithelium.