Essential roles of Tbx3 in embryonic skin development during epidermal stratification.
Essential roles of Tbx3 in embryonic skin development during epidermal stratification.
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Tbx3 在表皮分层过程中胚胎皮肤发育中的重要作用。
DOI：
10.1111/gtc.12476
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Fumiko Toyoshima
中科院分区：
文献类型：
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作者：
Ryo Ichijo;Yui Iizuka;Hirokazu Kubo;Fumiko Toyoshima
表皮细胞的逐步分化对复层上皮的发育至关重要，但其内在机制尚不清楚。在这里，我们表明Tbx 3，转录因子的T-box家族的成员，在这一机制中起着关键作用。Tbx 3在小鼠胚胎毛囊间表皮的基底细胞和基底上细胞中均有表达。表皮特异性Tbx 3条件性敲除（cKO）胚胎体积小，表皮较薄，屏障功能受损。在Tbx 3cKO表皮中，位于野生型胚胎基底层和基底上层的角蛋白5阳性未分化细胞仅位于基底层。此外，颗粒细胞标志物的mRNA表达水平在Tbx 3cKO表皮中增加，表明Tbx 3防止棘细胞的过早分化。我们进一步表明，Tbx 3保持了基底细胞的增殖潜力，并确保了它们的平面定向细胞分裂。此外，Tbx 3被证明是Hes 1表达所必需的，Hes 1是一种众所周知的Notch信号靶蛋白，对表皮发育至关重要。因此，我们建议，Tbx 3的功能上游的Hes 1调节增殖和分化的基底和基底上细胞在表皮发育。
Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T‐box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis‐specificTbx3conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function. In theTbx3cKO epidermis, keratin 5‐positive undifferentiated cells, which reside in both basal and suprabasal layers of wild‐type embryos, are localized exclusively in the basal layer. In addition, mRNA expression levels of granular cell markers are increased in theTbx3cKO epidermis, suggesting that Tbx3 prevents premature differentiation of spinous cells. We further show that Tbx3 maintains the proliferative potential of basal cells and ensures their planar‐oriented cell division. Moreover, Tbx3 is shown to be required for the expression of Hes1, a well‐known Notch signaling target protein that is essential for epidermal development. We therefore propose that Tbx3 functions upstream of Hes1 to regulate proliferation and differentiation of basal and suprabasal cells during epidermal development.