title: PTEN regulates lung endodermal morphogenesis through MEK/ERK pathway.
abstract: Pten is a multifunctional tumor suppressor. Deletions and mutations in the Pten gene have been associated with multiple forms of human cancers. Pten is a central regulator of several signaling pathways that influences multiple cellular functions. One such function is in cell motility and migration, although the precise mechanism remains unknown. In this study, we deleted Pten in the embryonic lung epithelium using Gata5-cre mice. Absence of Pten blocked branching morphogenesis and ERK and AKT phosphorylation at E12.5. In an explant model, Pten(Δ/Δ) mesenchyme-free embryonic lung endoderm failed to branch. Inhibition of budding in Pten(Δ/Δ) explants was associated with major changes in cell migration, while cell proliferation was not affected. We further examined the role of ERK and AKT in branching morphogenesis by conditional, endodermal-specific mutants which blocked ERK or AKT phosphorylation. MEK(DM/+); Gata5-cre (blocking of ERK phosphorylation) lung showed more severe phenotype in branching morphogenesis. The inhibition of budding was also associated with disruption of cell migration. Thus, the mechanisms by which Pten is required for early endodermal morphogenesis may involve ERK, but not AKT, mediated cell migration.
authors.affiliation: The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing 100191, PR China. Electronic address: ymxing@cau.edu.cn.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xing
authors.affiliation: The State Key Laboratory for Agro-biotechnology, China Agricultural University, Beijing 100191, PR China.
authors.forename: Runming
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, United States.
authors.forename: Changgong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, United States.
authors.forename: Parviz
authors.initials: P
authors.lastname: Minoo
mesh_terms: D000818:Animals; D002465:Cell Movement; D004707:Endoderm / Q000196:embryology* / Q000201:enzymology*; D004848:Epithelium / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D050992:GATA5 Transcription Factor / Q000378:metabolism; D017353:Gene Deletion; D019426:Integrases / Q000378:metabolism; D008168:Lung / Q000196:embryology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D009928:Organ Specificity; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D050992:GATA5 Transcription Factor; C494756:Gata5 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase
keywords: AKT; Branching morphogenesis; Cell migration; ERK; Endoderm; Lung morphogenesis; Pten