Specification of vertebral identity is coupled to Notch signalling and the segmentation clock
Specification of vertebral identity is coupled to Notch signalling and the segmentation clock
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DOI：
10.1242/dev.01030
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发表时间：
2004-03-01
期刊：
影响因子：
4.6
通讯作者：
Gossler, A
中科院分区：
文献类型：
--
作者：
Cordes, R;Schuster-Gossler, K;Gossler, A
为了进一步分析Notch信号在近轴中胚层模式化中的需求，我们产生了在近轴中胚层中表达Delta1的显性负性版本的转基因小鼠。如Hes5表达的丧失所指示的，在前体节中胚层中具有降低的Notch活性的转基因小鼠是存活的，并且在体节和椎骨中显示出与Notch信号传导在体节区室化中的已知作用一致的缺陷。此外，这些小鼠在12.5天的胚胎中表现出可变的表达性和椎体身份类似于同源异型转化的突变，以及Hox基因表达的微妙变化。仅携带一个内源性Delta1基因功能拷贝的小鼠也显示出下颈椎区域椎体身份的变化，表明Delta1的单倍不足。同样，在携带无效等位基因的振荡Lfng基因的小鼠，或在转基因小鼠中表达Lfng组成型的前体中胚层，脊椎身份发生变化，在颈部和胸部区域的节段数量减少，表明轴向身份的前移。总之，这些结果提供了遗传证据，精确调节水平的Notch活性以及循环Lfng活性是至关重要的位置规范的前后体轴在近轴中胚层。
To further analyse requirements for Notch signalling in patterning the paraxial mesoderm, we generated transgenic mice that express in the paraxial mesoderm a dominant-negative version of Delta1. Transgenic mice with reduced Notch activity in the presomitic mesoderm as indicated by loss of Hes5 expression were viable and displayed defects in somites and vertebrae consistent with known roles of Notch signalling in somite compartmentalisation. In addition, these mice showed with variable expressivity and penetrance alterations of vertebral identities resembling homeotic transformations, and subtle changes of Hox gene expression in day 12.5 embryos. Mice that carried only one functional copy of the endogenous Delta1 gene also showed changes of vertebral identities in the lower cervical region, suggesting a previously unnoticed haploinsufficiency for Delta1. Likewise, in mice carrying a null allele of the oscillating Lfng gene, or in transgenic mice expressing Lfng constitutively in the presomitic mesoderm, vertebral identities were changed and numbers of segments in the cervical and thoracic regions were reduced, suggesting anterior shifts of axial identity. Together, these results provide genetic evidence that precisely regulated levels of Notch activity as well as cyclic Lfng activity are critical for positional specification of the anteroposterior body axis in the paraxial mesoderm.