Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
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DOI：
10.1152/ajplung.00170.2003
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发表时间：
2004-04-01
影响因子：
4.9
通讯作者：
Brody, SL
中科院分区：
文献类型：
--
作者：
You, YJ;Huang, T;Brody, SL
未分化的气道上皮细胞向纤毛细胞定向分化所需的因素尚不清楚。细胞超微结构分析表明，纤毛细胞定型激活了一个多阶段的程序，包括纤毛前体蛋白的合成和大分子复合物的组装。Foxj1是一种在纤毛细胞中表达的f盒转录因子，在小鼠模型中通过基因缺失显示为纤毛形成所需。为了确定foxj1在指导纤毛细胞表型中的特定作用，我们评估了foxj1诱导纤毛发生和指导纤毛组装的能力。在野生型小鼠气道上皮细胞的原代培养模型中，foxj1的表达先于纤毛的出现，而在培养的foxj1缺失细胞中，纤毛没有发育。将foxj1传递到极化上皮细胞系和原代培养的肺泡上皮细胞不能促进纤毛发生。同样地，将foxj1传递给野生型气道上皮细胞并没有增加纤毛细胞的总数。相反，将foxj1传递到空细胞导致纤毛的出现。分析显示，在没有foxj1的情况下，空细胞含有纤毛前体基体，表明先前的承诺纤毛发生。然而，基底体在顶室中是无序的，并且未能与顶膜对接。foxj1在空细胞中的重建恢复了正常的基体组织，导致轴丝生长。因此，foxj1在后期纤毛发生中发挥作用，以调节促进先前致力于纤毛细胞表型的细胞中的基体对接和轴丝形成的程序。
Factors required for commitment of an undifferentiated airway epithelial cell to a ciliated cell are unknown. Cell ultrastructure analysis indicates ciliated cell commitment activates a multistage program involving synthesis of cilia precursor proteins and assembly of macromolecular complexes. Foxj1 is an f-box transcription factor expressed in ciliated cells and shown to be required for cilia formation by gene deletion in a mouse model. To identify a specific role for foxj1 in directing the ciliated cell phenotype, we evaluated the capacity of foxj1 to induce ciliogenesis and direct cilia assembly. In a primary culture model of wild-type mouse airway epithelial cells, foxj1 expression preceded the appearance of cilia and in cultured foxj1 null cells cilia did not develop. Delivery of foxj1 to polarized epithelial cell lines and primary cultured alveolar epithelial cells failed to promote ciliogenesis. Similarly, delivery of foxj1 to wild-type airway epithelial cells did not enhance the total number of ciliated cells. In contrast, delivery of foxj1 to null cells resulted in the appearance of cilia. Analysis revealed that, in the absence of foxj1, null cells contained cilia precursor basal bodies, indicating prior commitment to ciliogenesis. However, the basal bodies were disorganized within the apical compartment and failed to dock with the apical membrane. Reconstitution of foxj1 in null cells restored normal basal body organization, resulting in axoneme growth. Thus foxj1 functions in late-stage ciliogenesis to regulate programs promoting basal body docking and axoneme formation in cells previously committed to the ciliated cell phenotype.