TTF‐1 Regulates α5 nAChRs in Proximal Lung Epithelium During Lung Development

Abstract

Nicotinic acetylcholine receptors (nAChRs) are ligand‐gated ion channels formed by five similar subunits that combine to function in signal transduction, proliferation, and apoptosis. α5 nAChRs are structural subunits detected in many non‐neuronal tissues; however, their contributions to signaling during pulmonary development are unknown. α5 was assessed by immunohistochemistry in mouse lungs from embryonic day (E)13.5 to post‐natal day (PN)10. From E15.5 to E18.5, α5 was expressed in primitive airway epithelial cells and mesenchyme. α5 expression followed the proximal‐distal axis and was detected throughout the lung at PN5. Because perinatal expression was abundant in bronchiolar epithelium, we assessed transcriptional control of α5 in Beas2B cells, a human bronchiolar epithelial cell line, by TTF‐1, a transcription factor that controls pulmonary morphogenesis. TTF‐1 significantly increased α5 transcription by acting on the α5 promoter. Site‐directed mutagenesis revealed that TTF‐1 controlled transcription by binding to specific TTF‐1 response elements. These data demonstrate that α5 is specifically controlled in a temporal and spatial manner during pulmonary morphogenesis and that it may function in differentiating pulmonary epithelial cells involved in normal organogenesis. Supported by the Flight Attendants Medical Research Institute (FAMRI, PRR) and a BYU MEG Award (PRR).