E2f4 is required for normal development of the airway epithelium
E2f4 is required for normal development of the airway epithelium
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DOI：
10.1016/j.ydbio.2007.02.037
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发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Lees, Jacqueline A.
中科院分区：
文献类型：
--
作者：
Danielian, Paul S.;Kim, Carla F. Bender;Lees, Jacqueline A.
气道上皮细胞由专门的细胞类型组成，在保护肺免受环境损害方面发挥关键作用。小鼠呼吸道上皮的细胞组成是在发育过程中建立的，不同的细胞类型分布在沿着气道的特定区域。在这里，我们表明，E2 F4缺乏导致纤毛细胞从整个气道上皮和粘膜下腺体的鼻窦上皮的情况下。这种缺陷在E2 f4（-/-）小鼠的鼻上皮中特别显著，其中纤毛细胞被产生粘蛋白样物质的柱状分泌细胞取代。此外，在近端肺中，E2 f4缺失导致Clara细胞标志物表达减少，表明Clara细胞发育也受到影响。这些缺陷出现在胚胎发育过程中，在鼻上皮，似乎是独立的任何变化，细胞增殖，主要过程中调节的E2 f家族成员的转录因子。因此，我们得出结论，E2 F4是必要的，以确定适当的发展的气道上皮。重要的是，无纤毛细胞和过量粘液细胞的组合可以解释慢性鼻炎和对机会性感染的易感性增加，从而导致E2 f4突变小鼠的出生后致死性。(c)2007爱思唯尔公司All rights reserved.
The airway epithelium is comprised of specialized cell types that play key roles in protecting the lungs from environmental insults. The cellular composition of the murine respiratory epithelium is established during development and different cell types populate specific regions along the airway. Here we show that E2f4-deficiency leads to an absence of ciliated cells from the entire airway epithelium and the epithelium of the submucosal glands in the paranasal sinuses. This defect is particularly striking in the nasal epithelium of E2f4(-/-) mice where ciliated cells are replaced by columnar secretory cells that produce mucin-like substances. In addition, in the proximal lung, E2f4 loss causes a reduction in Clara cell marker expression indicating that Clara cell development is also affected. These defects arise during embryogenesis and, in the nasal epithelium, appear to be independent of any changes in cell proliferation, the principal process regulated by members of the E2f family of transcription factors. We therefore conclude that E2f4 is required to determine the appropriate development of the airway epithelium. Importantly, the combination of no ciliated cells and excess mucous cells can account for the chronic rhinitis and increased susceptibility to opportunistic infections that causes the postnatal lethality of E2f4 mutant mice. (c) 2007 Elsevier Inc. All rights reserved.