Journal article
Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
American journal of physiology. Lung cellular and molecular physiology, Vol.286(4), pp.L650-657
04/2004
DOI: 10.1152/ajplung.00170.2003
PMID: 12818891
Abstract
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.
Details
- Title: Subtitle
- Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
- Creators
- Yingjian You - Washington Univ. School of Medicine, Campus Box 8052, 660 South Euclid Ave., St. Louis, MO 63110, USATao HuangEdward J RicherJens-Erik Harboe SchmidtJoseph ZabnerZea BorokSteven L Brody
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.286(4), pp.L650-657
- DOI
- 10.1152/ajplung.00170.2003
- PMID
- 12818891
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- HL-72231 / NHLBI NIH HHS HL-63988 / NHLBI NIH HHS HL-56244 / NHLBI NIH HHS HL-62569 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/2004
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094213502771
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