Temporal Relationship between Primary and Motile Ciliogenesis in Airway Epithelial Cells
Temporal Relationship between Primary and Motile Ciliogenesis in Airway Epithelial Cells
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DOI：
10.1165/rcmb.2009-0328oc
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发表时间：
2010-12-01
影响因子：
6.4
通讯作者：
Brody, Steven L.
中科院分区：
文献类型：
--
作者：
Jain, Raksha;Pan, Jiehong;Brody, Steven L.
传统上纤毛分为活动纤毛和原发纤毛。活动纤毛仅限于特定的分化良好的上皮细胞群，包括气道、脑室和输卵管中的纤毛。初级纤毛是不运动的，孤立的结构，存在于许多细胞类型中，通常具有感觉功能，如视网膜和肾小管。初级纤毛也参与了基本发育过程的调节。对胚胎气道中初级纤毛的罕见描述使我们假设气道细胞中的初级纤毛在时间上与运动性纤毛发生有关。我们在小鼠和人类培养的未分化气道上皮细胞以及发育中的肺中发现了初级纤毛。气道中的孤立纤毛表达被认为是初级纤毛特有的蛋白质，包括多囊蛋白-1和多囊蛋白-2。气道上皮细胞分化的时间分析表明，具有原代纤毛的细胞获得了运动纤毛发生的标记，这表明运动纤毛细胞起源于原代纤毛细胞。运动纤毛发生需要Foxj1，而原发性纤毛发生不需要Foxj1， Foxj1的表达与运动纤毛出现前的初级纤毛缺失有关。在分化良好的气道上皮细胞中未发现初级纤毛。然而，损伤后，它们出现在上皮管腔层和基底细胞中。初生纤毛的短暂性，以及在气道上皮发育和修复过程中的时空表达模式，表明初生纤毛在气道上皮细胞分化过程中起着关键作用。
Cilia are traditionally classified as motile or primary. Motile cilia are restricted to specific populations of well-differentiated epithelial cells, including those in the airway, brain ventricles, and oviducts. Primary cilia are nonmotile, solitary structures that are present in many cell types, and often have sensory functions such as in the retina and renal tubules. Primary cilia were also implicated in the regulation of fundamental processes in development. Rare depictions of primary cilia in embryonic airways led us to hypothesize that primary cilia in airway cells are temporally related to motile ciliogenesis. We identified primary cilia in undifferentiated, cultured airway epithelial cells from mice and humans and in developing lungs. The solitary cilia in the airways express proteins considered unique to primary cilia, including polycystin-1 and polycystin-2. A temporal analysis of airway epithelial cell differentiation showed that cells with primary cilia acquire markers of motile ciliogenesis, suggesting that motile ciliated cells originate from primary ciliated cells. Whereas motile ciliogenesis requires Foxj1, primary ciliogenesis does not, and the expression of Foxj1 was associated with a loss of primary cilia, just before the appearance of motile cilia. Primary cilia were not found in well-differentiated airway epithelial cells. However, after injury, they appear in the luminal layer of epithelium and in basal cells. The transient nature of primary cilia, together with the temporal and spatial patterns of expression in the development and repair of airway epithelium, suggests a critical role of primary cilia in determining outcomes during airway epithelial cell differentiation.