DIFFERENTIALLY REGULATED EPITHELIAL EXPRESSION OF AN EPH FAMILY TYROSINE KINASE (FHEK2) DURING TRACHEAL SURFACE AIRWAY AND SUBMUCOSAL GLANDDEVELOPMENT

A ferret model was used to evaluate the potential role of an Eph famil y tyrosine kinase (fHek2) in tracheal development of surface airway ep ithelium and submucosal glands. A partial 2.6-kb cDNA fragment of fHek 2 was isolated from a ferret tracheal/lung cDNA library. Sequence anal ysis demonstrated that this gene is the ortholog to the previously clo ned human Hek2 gene. In situ hybridization analysis of fHek2 mRNA expr ession on ferret tracheal developmental time points revealed an expres sion 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 glan ds at 3-day postnatal time points demonstrated little fHek2 mRNA expre ssion. However, expression of fHek2 significantly increased more than 4-fold over the course of gland development to adulthood. These findin gs, which demonstrate a uniquely regulated pattern of Mek2 mRNA expres sion between surface airway epithelium and submucosal glands, have imp lications 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 di fferentiation in the lung and how these processes are abnormally regul ated in hypersecretory diseases such as chronic bronchitis, asthma, an d cystic fibrosis.