Study On The Function Of Isl1 In The Development Of Mammalian Lung

Lung is the primary organ of human respiratory system and situated with in the thoracic cavity of the chest.It is mainly composed of epithelium,bronchus,alveoli as well as other tissues to support the exchange of gas between the body and the external environment.Abnormal lung development can lead to a variety of serious defects,such as congenital cystic lung disease,lung dysplasia,and bronchopulmonary dysplasia.The normal lung development process is critical to survival after birth.To determine Isl1 function in the lung,we destroy Isl1 structure by crossing Shh ^Cremice to Isl1^flox/floxmice to obtain mutant mice(Shh ^Cre;Isl1^flox/flox)that were conditionally knocked out Isl1 in lung epithelial cells.We found Isl1 mutant mice were fatal at birth,and HE staining on P0 lung showing the alveoli is keeping closed.Additionally,cell proliferation and apoptosis were detected by immunohistological staining.Isl1 mutant mice had abnormally increased cell proliferation in the lungs from E16.5,but there was no difference in apoptosis.RNA-Seq sequencing was used to screen possible targets of Isl1,and the differentially expressed genes were further verified by in situ hybridization experiments.The expression of epithelial cell markers for AT2 and AT1 like SLC34A2,SPC,and AQP5 were significantly downregulated in P0mutant mice,and similar trend has been found in the ligand Dlk1 in Notch pathway as well as proximal progenitor cells marker Sox2.In summary,Isl1 depletion will impair lung development,and the differentiation process of epithelial cells may be inhibited.The specific molecular mechanism remains elusive and needs further study.