ELASTOGENESIS IN THE DEVELOPING CHICK LUNG IS TRANSCRIPTIONALLY REGULATED

The overall goals of this study were to establish the level at which e lastin gene expression is regulated during chick lung embryogenesis an d to identify the temporal and spatial relationships among elastogenes is, smooth muscle cell differentiation, and cell proliferation. A comp arison of lung elastin mRNA and transcriptional levels during embryoge nesis shows that elastin expression is developmentally regulated at th e transcriptional level. The increase in elastogenic activity occurs d uring the late stages of lung embryogenesis and coincides with termina l maturation of the tertiary bronchi. In situ hybridization analysis d emonstrates that the increase in elastin mRNA expression is confined t o the tertiary bronchial respiratory subunits, connective tissue septa , and supporting vasculature of the lung parenchyma. Immunohistochemic al localization of smooth muscle cell alpha-actin and tropoelastin sug gests that alpha-actin-immunoreactive cells of the lung parenchyma are a major contributor to the increase in elastin expression during embr yogenesis. This observation is also reflected by Northern blot analysi s, which demonstrates a temporal coincidence in the increase of both a lpha-actin and elastin mRNA levels. Histone mRNA expression, which was used as an index of cellular proliferation, reveals a level and spati al pattern inversely related to that of the elastin transcript. Tissue transfections of chick lungs isolated from 18-day embryos with variou s elastin gene deletion/reporter constructs illustrate that the elasti n promoter is not promiscuous within a tissue environment and that seq uences spanning the -500 to +2 region are capable of directing promote r activity spatially comparable to the endogenous elastin gene. Dev. D yn. 1998;213:170-181. (C) 1998 Wiley-Liss, Inc.