Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis
Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis
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DOI：
10.1038/sj.jid.5701113
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发表时间：
2008-04-01
影响因子：
6.5
通讯作者：
Watt, Fiona M.
中科院分区：
文献类型：
--
作者：
Estrach, Soline;Cordes, Ralf;Watt, Fiona M.
Notch配体Delta1(DLL1)在人毛囊间皮细胞(IFE)中表达，调节培养的人角质形成细胞的分化和黏附。然而，在小鼠表皮中删除DLL1的后果还没有得到检验。在这里，我们报道了在胚胎小鼠皮肤中，Dll1由IFE基底层、真皮乳头和毛球中的角质形成细胞斑块表达。在一个存活到出生的Dll1低晶型突变体中，毛囊正常形成，但IFE的增殖和厚度增加。在角蛋白-5(K5)启动子控制下表达的Cre重组酶缺失DLL1导致出生后第一个生长期延迟，但随后的毛发周期是正常的。与低畸形期一样，IFE的增殖受到刺激，K10和K17的表达受到干扰。年龄较大的小鼠患上了含有IFE分化成分的肿瘤。从K5Cre x Dll1(FLOX/FLOX)表皮培养的角质形成细胞出现一过性增殖增加，随后整合素表达减少，终末分化增加。这些结果表明，DLL1有助于控制IFE的增殖和分化，而Jagged1调节毛囊的分化。
The Notch ligand Delta1 (Dll1) is expressed in human interfollicular epidermis (IFE) and regulates differentiation and adhesion of cultured human keratinocytes. However, the consequences of deleting Dll1 in mouse epidermis have not been examined. Here, we report that in embryonic mouse skin Dll1 is expressed by patches of keratinocytes in the basal layer of the IFE and in the dermal papilla and hair bulb. In a Dll1 hypomorph mutant that survives until birth, hair follicles formed normally but proliferation and thickness of the IFE were increased. Deletion of Dll1 using Cre recombinase expressed under the control of the keratin- 5 (K5) promoter resulted in a delay in the first postnatal anagen, but subsequent hair cycles were normal. As in the hypomorph, IFE proliferation was stimulated and expression of K10 and K17 was disturbed. Older mice developed tumors with elements of IFE differentiation. Keratinocytes cultured from K5Cre x Dll1(flox/flox) epidermis showed a transient increase in proliferation, with a subsequent decrease in integrin expression and increased terminal differentiation. These results demonstrate that Dll1 contributes to the control of proliferation and differentiation in IFE, whereas Jagged1 regulates hair follicle differentiation.