Thomas A. Neff lecture. Application of expression profiling to the developing lung: identification of putative regulatory networks controlling matrix production.

Abstract

If we hope to repair damaged lung tissue associated with a variety of acquired and developmental diseases, we must first gain a full appreciation of normal lung development. As an approach, we have utilized Affymetrix (Santa Clara, CA) high-density, oligonucleotide-based microarrays to generate an expression profile of the entire process of rodent lung development, which will be made publicly available. Our initial results were internally consistent and correlated closely with those generated with standard expression techniques such as Northern hybridization. We have verified known expression of genes, found other genes with previously unsuspected expression during lung development, as well as uncovered many expressed sequence tags whose role in lung development awaits further study. Data mining reveals close relationships of expression profiles between specific genes, suggesting novel regulatory relationships. In the future, application of these methods to the study of gene-targeted mice with abnormal lung development should uncover pathways of airway and alveolar development. Ultimately, expression profiling of diseased lungs might allow us to understand why the lung fails to repair, and strategies to influence repair might become apparent.