Forkhead transcription factor HFH-4 expression is temporally related to ciliogenesis

Members of the forkhead/winged-helix family of transcription factors are ex pressed in tissue-specific patterns and play critical roles in development and cell differentiation. The expression of forkhead family member hepatocy te nuclear factor-3/forkhead homologue 4 (HFH-4) has been localized by RNA- blot analysis and in situ hybridization to the proximal airway of the lung (trachea, bronchi, and bronchioles) with onset at mouse embryonic day (E 14 .5 and is present in the choroid plexus, ependymal cells, oviduct, and test is. We hypothesized that the restricted expression of HFH-4 messenger RNA s uggests a function common to these tissues and therefore a cell-specific ro le for HFH-4. Accordingly, an anti-HFH-4 antibody was generated and used fo r cell-specific localization of protein expression to begin to identify the functions of HFH-4. We found HFH-4 expression in proximal airway ciliated epithelial cells, but not Clara cells or alveolar epithelial cells. HFH-4 w as also expressed in ciliated epithelial cells of the nose and paranasal si nuses. choroid plexus, ependyma, and oviduct. In developing mouse lung, HFH -4 expression was initially detected in airway epithelial cells at E15.5, b efore the appearance of cilia, and at later stages was localized to epithel ial cells with cilia. In the testis, HFH-4 expression in spermatids was coi ncident with stage-specific generation of flagella. The temporal relationsh ip of HFH-4 expression to the development of cilia and flagella, and the re stricted expression in ciliated epithelial cells? suggest that this transcr iption factor has a role in regulation and maintenance of the ciliated cell phenotype in epithelial cells.