Nair Mahalakshmi, Teng Andy, Bilanchone Virginia, Agrawal Anshu, Li Baoan, Dai Xing
Department of Biological Chemistry, University of California, Irvine, 92697, USA.
J Cell Biol. 2006 Apr 24;173(2):253-64. doi: 10.1083/jcb.200508196.
Transcriptional control plays a key role in regulating epidermal proliferation and differentiation. Although ample information has been obtained on how epidermal homeostasis is controlled in adult skin, less is known about the control of proliferation/differentiation of epidermal stem/progenitor cells in the developing embryo. Ovol1, encoding a zinc finger protein homologous to Drosophila melanogaster Ovo, is expressed in embryonic epidermal progenitor cells that are transiting from proliferation to terminal differentiation. In this study, we demonstrate a function for Ovol1 in interfollicular epidermal development. In its absence, developing epidermis fails to properly restrict the proliferative potential of progenitor cells, and cultured keratinocytes fail to efficiently undergo growth arrest in response to extrinsic growth-inhibitory signals. We present molecular evidence that c-myc expression is up-regulated in Ovol1-deficient suprabasal cells and that Ovol1 represses c-myc transcription by directly binding to its promoter. Collectively, our findings indicate that Ovol1 is required for proliferation exit of committed epidermal progenitor cells and identify c-myc as an Ovol1 target.
转录调控在调节表皮增殖和分化中起关键作用。尽管在成人皮肤中表皮稳态如何受到控制方面已经获得了大量信息，但对于发育中胚胎表皮干细胞/祖细胞增殖/分化的控制了解较少。Ovol1编码一种与果蝇Ovo同源的锌指蛋白，在从增殖过渡到终末分化的胚胎表皮祖细胞中表达。在本研究中，我们证明了Ovol1在毛囊间表皮发育中的功能。在其缺失时，发育中的表皮无法正确限制祖细胞的增殖潜能，并且培养的角质形成细胞对外源生长抑制信号无法有效发生生长停滞。我们提供了分子证据，表明在Ovol1缺陷的基底层以上细胞中c-myc表达上调，并且Ovol1通过直接结合其启动子来抑制c-myc转录。总体而言，我们的研究结果表明Ovol1是已分化的表皮祖细胞退出增殖所必需的，并确定c-myc为Ovol1的一个靶点。
