Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon
Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon
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DOI：
10.1242/dev.024570
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发表时间：
2008-12-01
期刊：
影响因子：
4.6
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
--
作者：
Kawaguchi, Daichi;Yoshimatsu, Takeshi;Gotoh, Yukiko
在哺乳动物脑发育的神经发生阶段，只有神经前体细胞（NPC）的亚群分化为神经元。这种选择的机制尚不清楚。在这里，我们提供的证据表明，Notch-Delta通路在这种选择中发挥了重要作用，在发展中的小鼠端脑。我们发现Notch配体δ样1（Dll 1）和Notch 1的活性形式的表达模式是相互排斥的，并在端脑的脑室区分离成不同的NPC亚群。当Dll 1过表达在一个小的，但不是一个大的，比例的NPC，这些细胞在体外和体内进行神经元分化。当细胞在体外培养中以较低密度接种时，这种Dll 1诱导的神经元分化不会发生。重要的是，在一小部分NPC中Dll 1基因的条件性缺失减少了体内神经发生，而在大部分NPC中的缺失促进了过早的神经发生。这些结果支持这样的观点，即不同水平的Dll 1表达通过细胞-细胞相互作用决定NPC的命运，最有可能是通过Notch-Delta侧向抑制信号传导途径，从而有助于分化细胞的选择。
During the neurogenic phase of mammalian brain development, only a subpopulation of neural precursor cells (NPCs) differentiates into neurons. The mechanisms underlying this selection remain unclear. Here we provide evidence that the Notch-Delta pathway plays an important role in this selection in the developing mouse telencephalon. We found that the expression patterns of the Notch ligand delta-like 1 (Dll1) and of the active form of Notch1 were mutually exclusive and segregated into distinct NPC subpopulations in the ventricular zone of the telencephalon. When Dll1 was overexpressed in a small, but not a large, proportion of NPCs, these cells underwent neuronal differentiation in vitro and in vivo. This Dll1-induced neuronal differentiation did not occur when cells were plated at lower densities in an in vitro culture. Importantly, conditional deletion of the Dll1 gene in a small proportion of NPCs reduced neurogenesis in vivo, whereas deletion in a large proportion promoted premature neurogenesis. These results support the notion that different levels of Dll1 expression determine the fate of NPCs through cell-cell interactions, most likely through the Notch-Delta lateral inhibitory signaling pathway, thus contributing to the selection of differentiating cells.