Differentially regulated epithelial expression of an Eph family tyrosine kinase (fHek2) during tracheal surface airway and submucosal gland development.

A ferret model was used to evaluate the potential role of an Eph family tyrosine kinase (fHek2) in tracheal development of surface airway epithelium and submucosal glands. A partial 2.6-kb cDNA fragment of fHek2 was isolated from a ferret tracheal/lung cDNA library. Sequence analysis demonstrated that this gene is the ortholog to the previously cloned human Hek2 gene. In situ hybridization analysis of fHek2 mRNA expression on ferret tracheal developmental time points revealed an expression pattern within a subset of surface airway epithelial cells which remained relatively constant throughout tracheal development (from -2 d in utero to adult). In contrast, developing tracheal submucosal glands at 3-day postnatal time points demonstrated little fHek2 mRNA expression. However, expression of fHek2 significantly increased more than 4-fold over the course of gland development to adulthood. These findings, which demonstrate a uniquely regulated pattern of fHek2 mRNA expression between surface airway epithelium and submucosal glands, have implications on regulatory processes which control differentiation and/or maturation of secretory structures in the lung. Such findings may be useful in further delineating the mechanisms which control cellular differentiation in the lung and how these processes are abnormally regulated in hypersecretory diseases such as chronic bronchitis, asthma, and cystic fibrosis.