Msx homeobox genes inhibit differentiation through upregulation of cyclin D1.
Msx homeobox genes inhibit differentiation through upregulation of cyclin D1.
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发表时间：
2001-06
期刊：
影响因子：
4.6
通讯作者：
G. Hu;Hansol Lee;Sandy M. Price;M. Shen;C. Abate-Shen
中科院分区：
文献类型：
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作者：
G. Hu;Hansol Lee;Sandy M. Price;M. Shen;C. Abate-Shen
在发育过程中，组织的图案化和形态发生通过控制细胞增殖和分化而密切协调。我们描述了一种机制，脊椎动物Msx同源框基因抑制细胞分化的细胞周期的调节。我们发现，Msx1通过逆转录病毒基因转移的错误表达抑制多种间充质和上皮祖细胞类型的分化培养。Msx1的这种活性与其上调细胞周期蛋白D1表达和Cdk4活性的能力相关，而Msx1对细胞增殖的影响最小。在小鼠乳腺肿瘤病毒长末端重复序列（MMTV LTR）控制下表达Msx 1的转基因小鼠在妊娠期间显示乳腺上皮分化受损，这伴随着细胞周期蛋白D1表达水平升高。我们建议Msx1基因表达维持细胞周期蛋白D1的表达，并防止退出细胞周期，从而抑制祖细胞的终末分化。我们的模型提供了一个框架，以调和Msx和其他同源异型盒基因的突变表型与它们的功能，作为调节细胞增殖和分化在胚胎发生过程中。
During development, patterning and morphogenesis of tissues are intimately coordinated through control of cellular proliferation and differentiation. We describe a mechanism by which vertebrate Msx homeobox genes inhibit cellular differentiation by regulation of the cell cycle. We show that misexpression of Msx1 via retroviral gene transfer inhibits differentiation of multiple mesenchymal and epithelial progenitor cell types in culture. This activity of Msx1 is associated with its ability to upregulate cyclin D1 expression and Cdk4 activity, while Msx1 has minimal effects on cellular proliferation. Transgenic mice that express Msx1 under the control of the mouse mammary tumor virus long terminal repeat (MMTV LTR) display impaired differentiation of the mammary epithelium during pregnancy, which is accompanied by elevated levels of cyclin D1 expression. We propose that Msx1 gene expression maintains cyclin D1 expression and prevents exit from the cell cycle, thereby inhibiting terminal differentiation of progenitor cells. Our model provides a framework for reconciling the mutant phenotypes of Msx and other homeobox genes with their functions as regulators of cellular proliferation and differentiation during embryogenesis.