Amin Shilu, Neijts Roel, Simmini Salvatore, van Rooijen Carina, Tan Sander C, Kester Lennart, van Oudenaarden Alexander, Creyghton Menno P, Deschamps Jacqueline
Hubrecht Institute and UMC Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Hubrecht Institute and UMC Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Cell Rep. 2016 Dec 20;17(12):3165-3177. doi: 10.1016/j.celrep.2016.11.069.
In vertebrate embryos, anterior tissues are generated early, followed by the other axial structures that emerge sequentially from a posterior growth zone. The genetic network driving posterior axial elongation in mice, and its disturbance in mutants with posterior truncation, is not yet fully understood. Here, we show that the combined expression of Cdx2 and T Brachyury is essential to establish the core signature of posterior axial progenitors. Cdx2 and T Brachyury are required for extension of a similar trunk portion of the axis. Simultaneous loss of function of these two genes disrupts axial elongation to a much greater extent than each single mutation alone. We identify and validate common targets for Cdx2 and T Brachyury in vivo, including Wnt and Fgf pathway components active in the axial progenitor niche. Our data demonstrate that integration of the Cdx/Hox and T Brachyury transcriptional networks controls differential axial growth during vertebrate trunk elongation.
在脊椎动物胚胎中，前部组织早期形成，随后其他轴向结构从后部生长区依次出现。驱动小鼠后部轴向伸长的遗传网络及其在后部截断突变体中的紊乱情况尚未完全了解。在这里，我们表明Cdx2和T短尾的联合表达对于建立后部轴向祖细胞的核心特征至关重要。Cdx2和T短尾是轴的类似躯干部分延伸所必需的。这两个基因的功能同时丧失比单独的每个单一突变更严重地破坏轴向伸长。我们在体内鉴定并验证了Cdx2和T短尾的共同靶点，包括在轴向祖细胞生态位中活跃的Wnt和Fgf信号通路成分。我们的数据表明，Cdx/Hox和T短尾转录网络的整合控制脊椎动物躯干伸长过程中的差异轴向生长。
