Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells.
نویسندگان
چکیده
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.
منابع مشابه
The role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
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 multi-stage 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...
متن کاملFoxj1 is required for apical localization of ezrin in airway epithelial cells.
Establishment and maintenance of epithelial cell polarity depend on cytoskeletal organization and protein trafficking to polarized cortical membranes. ERM (ezrin, radixin, moesin) family members link polarized proteins with cytoskeletal actin. Although ERMs are often considered to be functionally similar, we found that, in airway epithelial cells, apical localization of ERMs depend on cell diff...
متن کاملRFX3 Modulation of FOXJ1 regulation of cilia genes in the human airway epithelium
BACKGROUND Ciliated cells play a central role in cleansing the airways of inhaled contaminants. They are derived from basal cells that include the airway stem/progenitor cells. In animal models, the transcription factor FOXJ1 has been shown to induce differentiation to the ciliated cell lineage, and the RFX transcription factor-family has been shown to be necessary for, but not sufficient to in...
متن کاملCALL FOR PAPERS Stem Cells in Lung Biology Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
Yingjian You, Tao Huang, Edward J. Richer, Jens-Erik Harboe Schmidt, Joseph Zabner, Zea Borok, and Steven L. Brody Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; Department of Biochemistry and Molecular Biology and Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033; Depa...
متن کاملIL-13 regulates cilia loss and foxj1 expression in human airway epithelium.
Mucociliary clearance is essential to the defense mechanisms of the respiratory system. Loss of normal mucociliary clearance contributes to the pathogenesis of genetic and acquired lung diseases. Treatment of cultured differentiated human airway epithelial tissue with IL-13 resulted in a loss of ciliated epithelial cells and an increase in mucus-secreting cells. The loss of ciliated cells was c...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- American journal of physiology. Lung cellular and molecular physiology
دوره 286 4 شماره
صفحات -
تاریخ انتشار 2004