Pulmonary Mesenchymal Differentiation

The conductive and respiratory epithelium of the lung is surrounded by mesenchyme and vascular tissue. The pulmonary vasculature is critical for the lung's respiratory function. Disrupted pulmonary microvasculature development impairs growth and differentiation of the lung, which is associated with perinatal lethality.

We have generated a model in which the deletion of Wls (a gene that mediates Wnt ligand secretion) in the developing lung's epithelium results in dysmorphic microvasculature. Our studies showed that Wnt ligands' secretion from the pulmonary epithelium is required for the differentiation of endothelium and patterning of the microvasculature. Our goals are defining the molecular mechanisms mediating pulmonary endothelial cell differentiation and determining the specific role of diverse Wnt ligands in pulmonary vascular development.

The mesenchyme gives rise to diverse cell types, including smooth muscle cells, fibroblasts, and pericytes. We are currently studying how the mesenchyme influences the shape, the number of lobes, and the lungs' left-right asymmetry. For this purpose, we utilize different mouse models with deficiencies in growth and lobe formation. The studies will contribute to better diagnosis and treatment of pulmonary diseases affecting premature babies and the neonate population.