CDX4 regulates the progression of neural maturation in the spinal cord
CDX4 regulates the progression of neural maturation in the spinal cord
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DOI：
10.1016/j.ydbio.2019.02.014
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发表时间：
2019-05-15
影响因子：
2.7
通讯作者：
Skromne, Isaac
中科院分区：
文献类型：
--
作者：
Joshi, Piyush;Darr, Andrew J.;Skromne, Isaac
细胞沿着不同的谱系途径前进是细胞外信号网络和细胞内转录因子网络之间的合作努力。在脊椎动物脊髓中，成纤维细胞生长因子、神经营养因子和维甲酸信号通路通过调节一个鲜为人知的转录因子基因调控网络来调节神经前体细胞从尾端到嘴端的渐进性成熟。我们已经在鸡的前神经管中绘制出了这个基因调控网络，发现CDX4是一个双重功能的核心成分，同时调节细胞潜能的逐渐丧失和分化状态的获得：在从尾端到嘴端的方向上，CDX4抑制早期神经分化标记Nkx1.2，促进晚期神经分化标记Pax6。值得注意的是，CDX4通过阻断Ngn2的激活来阻止PAX6依赖的神经分化。CDX4对Pax6的这种调节通过维甲酸信号被限制在吻侧前神经管。综上所述，我们的结果表明，在脊髓中，CDX4是基因调控网络的一部分，控制着神经前体成熟过程中状态从高到低的顺序和渐进转换。鉴于CDX众所周知参与了HOX基因的调控，我们认为CDX因子在脊髓发育过程中协调神经前体细胞的成熟和轴向规范。
The progression of cells down different lineage pathways is a collaborative effort between networks of extra cellular signals and intracellular transcription factors. In the vertebrate spinal cord, FGF, Wnt and Retinoic Acid signaling pathways regulate the progressive caudal-to-rostral maturation of neural progenitors by regulating a poorly understood gene regulatory network of transcription factors. We have mapped out this gene regulatory network in the chicken pre-neural tube, identifying CDX4 as a dual-function core component that simultaneously regulates gradual loss of cell potency and acquisition of differentiation states: in a caudal-to-rostral direction, CDX4 represses the early neural differentiation marker Nkx1.2 and promotes the late neural differentiation marker Pax6. Significantly, CDX4 prevents premature PAX6-dependent neural differentiation by blocking Ngn2 activation. This regulation of CDX4 over Pax6 is restricted to the rostral pre-neural tube by Retinoic Acid signaling. Together, our results show that in the spinal cord, CDX4 is part of the gene regulatory network controlling the sequential and progressive transition of states from high to low potency during neural progenitor maturation. Given CDX well-known involvement in Hox gene regulation, we propose that CDX factors coordinate the maturation and axial specification of neural progenitor cells during spinal cord development.