High commitment of embryonic keratinocytes to terminal differentiation through a notch1-caspase 3 regulatory mechanism
High commitment of embryonic keratinocytes to terminal differentiation through a notch1-caspase 3 regulatory mechanism
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DOI：
10.1016/s1534-5807(04)00098-x
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发表时间：
2004-04-01
影响因子：
11.8
通讯作者：
Dotto, GP
中科院分区：
文献类型：
--
作者：
Okuyama, R;Nguyen, BC;Dotto, GP
胚胎细胞在发育过程中具有较高的生长/分化潜能，是器官形态发生和扩张所必需的。然而，由于胚胎上皮细胞的分离和培养困难，人们对其内在特性知之甚少。我们在这里报道，E15.5小鼠胚胎的纯角质细胞群体比新生细胞更早地发生不可逆转的分化。Notch信号可以促进角质细胞分化，在胚胎角质细胞和表皮中表达上调，而caspase 3的表达升高，我们将其确定为Notch1的转录靶点，这在一定程度上解释了胚胎角质细胞向终末分化的高度承诺。在体内，caspase 3的缺乏导致卵泡间胚胎角质形成细胞增殖增加和分化减少，同时PKC-delta的激活降低，PKC-delta是一种caspase 3底物，作为角质形成细胞分化的积极调节因子。因此，Notch1-caspase 3调控机制是胚胎角化细胞向终末分化的内在高度承诺的基础。
Embryonic cells are expected to possess high growth/ differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.