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The conductive and respiratory epithelium of the lung is surrounded by the mesenchyme. The pulmonary mesenchyme gives rise to diverse cell types, including smooth muscle cells, fibroblasts and perycites. Embedded in the mesenchyme is the endothelium, which gives rise to the pulmonary vasculature necessary for the respiratory function of the lung. Disrupted development of the pulmonary microvasculature results in pathological conditions, including hypoplastic lungs, which are associated with perinatal lethality.
We have generated a model in which the deletion of Wls (gene that mediates Wnt ligand secretion) in the epithelium of the developing lung results in dysmorphic microvasculature. Our studies showed that secretion of Wnt ligands from the pulmonary epithelium is required for differentiation of endothelium and patterning of the microvasculature. Our goals are to define the molecular mechanisms mediating pulmonary endothelial cell differentiation, and to determine the specific role of diverse Wnt ligands in pulmonary vascular development. This knowledge is required for better diagnosis and treatment of pulmonary diseases affecting premature babies and neonate population.
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