Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells

被引:161
作者
You, YJ
Huang, T
Richer, EJ
Schmidt, JEH
Zabner, J
Borok, Z
Brody, SL
机构
[1] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA
[2] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA
[3] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
[4] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[5] Univ So Calif, Will Rogers Inst Pulm Res Ctr, Los Angeles, CA 90033 USA
[6] Univ So Calif, Dept Med, Los Angeles, CA 90033 USA
关键词
airway; basal body; cilia; differentiation; mouse;
D O I
10.1152/ajplung.00170.2003
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:L650 / L657
页数:8
相关论文
共 38 条
[31]  
Stephens RE, 1998, CELL MOTIL CYTOSKEL, V40, P379, DOI 10.1002/(SICI)1097-0169(1998)40:4<379::AID-CM6>3.0.CO
[32]  
2-6
[33]   HNF-3/forkhead homologue-4 influences lung morphogenesis and respiratory epithelial cell differentiation in vivo [J].
Tichelaar, JW ;
Lim, L ;
Costa, RH ;
Whitsett, JA .
DEVELOPMENTAL BIOLOGY, 1999, 213 (02) :405-417
[34]  
Tsakraklides V, 1999, J CELL SCI, V112, P2853
[35]   Increasing epithelial junction permeability enhances gene transfer to airway epithelia in vivo [J].
Wang, GS ;
Zabner, J ;
Deering, C ;
Launspach, J ;
Shao, J ;
Bodner, M ;
Jolly, DJ ;
Davidson, BL ;
McCray, PB .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 22 (02) :129-138
[36]   ADENOVIRUS-MEDIATED GENE-TRANSFER FOR CYSTIC-FIBROSIS .A. SAFETY OF DOSE AND REPEAT ADMINISTRATION IN THE NASAL EPITHELIUM PART .B. CLINICAL EFFICACY IN THE MAXILLARY SINUS [J].
WELSH, MJ ;
ZABNER, J ;
GRAHAM, SM ;
SMITH, AE ;
MOSCICKI, R ;
WADSWORTH, S .
HUMAN GENE THERAPY, 1995, 6 (02) :205-218
[37]   Expression of primary cilia in mammalian cells [J].
Wheatley, DN ;
Wang, AM ;
Strugnell, GE .
CELL BIOLOGY INTERNATIONAL, 1996, 20 (01) :73-81
[38]   Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population [J].
You, YJ ;
Richer, EJ ;
Huang, T ;
Brody, SL .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2002, 283 (06) :L1315-L1321