Department of Cell Biology, and Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, USA.
Nat Commun. 2010 Apr 12;1(1):9. doi: 10.1038/ncomms1008.
During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal and lineage decisions are incompletely understood. In this study, we show that their survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 and Sox12. The more SoxC alleles that are deleted in mouse embryos, the more severe and widespread organ hypoplasia is. SoxC triple-null embryos die at midgestation unturned and tiny, with normal patterning and lineage specification, but with massively dying neural and mesenchymal progenitor cells. Specific inactivation of SoxC genes in neural and mesenchymal cells leads to selective apoptosis of these cells, suggesting SoxC cell-autonomous roles. Tead2 functionally interacts with SoxC genes in embryonic development, and is a direct target of SoxC proteins. SoxC genes therefore ensure neural and mesenchymal progenitor cell survival, and function in part by activating this transcriptional mediator of the Hippo signalling pathway.
在器官发生过程中，神经和间质祖细胞产生许多细胞谱系，但它们自我更新和谱系决定的分子要求尚不完全清楚。在这项研究中，我们表明它们的存活严重依赖于 SoxC 转录因子 Sox4、Sox11 和 Sox12 的冗余作用。在小鼠胚胎中删除的 SoxC 等位基因越多，器官发育不全的情况就越严重和广泛。 SoxC 三重缺失的胚胎在中期死亡，不成形且很小，具有正常的模式和谱系特异性，但大量的神经和间充质祖细胞死亡。 SoxC 基因在神经和间充质细胞中的特异性失活导致这些细胞的选择性凋亡，表明 SoxC 细胞自主作用。Tead2 在胚胎发育中与 SoxC 基因具有功能相互作用，是 SoxC 蛋白的直接靶标。因此，SoxC 基因确保神经和间充质祖细胞的存活，并通过激活 Hippo 信号通路的这种转录中介物部分发挥作用。
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