The role of Sonic Hedgehog in postnatal mouse lung development

Hedgehog signaling pathway is a main regulator, in the normal development of many tissues such as lung in most animals. As a key protein of hedgehog signaling pathway, sonic hedgehog (Shh) has shown to be critical regulator in the branching morphogenesis of the lung. Until now the role of Shh in all cell types responsible for the alveolarization is pretty unknown. Since Shh has been found to have a critical role in tissue development, acting as a morphogen involved in tissue patterning, we hypothesize that Shh expression is critical for the regulation of the lipofibroblast and myofibroblast phenotypes, both of which are necessary elements for septation. We identified shh as being overexpressed in the lung tissue at the onset and during alveolarization, we will investigate its role in septation in vivo. We address gain of Shh function that will be achieved by doxycycline-inducible lung epithelial cell-targeted over-expression of Shh by using the tet-on system. To investigate the role of Shh in all tissue types of the lung we aim for global conditional Shh deletion by using a cre/loxP system. In addition cyclopamine will be used in order to study the role of Shh signaling pathway during alveolarization.