Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch
Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch
复制标题
DOI：
10.1038/ng1894
复制
发表时间：
2006-11-01
期刊：
影响因子：
30.8
通讯作者：
Dixon, Michael J.
中科院分区：
文献类型：
--
作者：
Richardson, Rebecca J.;Dixon, Jill;Dixon, Michael J.
表皮是一种高度组织化的结构，其完整性对于保护生物体至关重要（1）。这种组织的发育和随后的维持关键取决于常驻干细胞群体的增殖和分化之间的复杂平衡（1，2）;然而，控制体内增殖-分化开关的信号仍然难以捉摸（3）。在这里，我们表明，小鼠携带的干扰素调节因子6（Irf 6），在人类先天性疾病货车der Woude综合征和腘翼状胬肉综合征的基因突变的同源物纯合错义突变，有一个过度增生的表皮，未能进行终末分化，导致软组织融合。我们进一步证明，小鼠是复合杂合子突变的Irf 6和基因编码的细胞周期调节蛋白分层（Sfn;也称为14-3-3西格玛）表现出类似的缺陷角化上皮。我们的研究结果表明，Irf 6是角质形成细胞增殖分化开关的关键决定因素，Irf 6和Sfn在这个过程中相互作用。
The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism(1). Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population(1,2); however, the signals controlling the proliferation-differentiation switch in vivo remain elusive(3). Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3 sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process.