title: Nubp1 is required for lung branching morphogenesis and distal progenitor cell survival in mice.
abstract: The lung is a complex system in biology and medicine alike. Whereas there is a good understanding of the anatomy and histology of the embryonic and adult lung, less is known about the molecular details and the cellular pathways that ultimately orchestrate lung formation and affect its health. From a forward genetic approach to identify novel genes involved in lung formation, we identified a mutated Nubp1 gene, which leads to syndactyly, eye cataract and lung hypoplasia. In the lung, Nubp1 is expressed in progenitor cells of the distal epithelium. Nubp1(m1Nisw) mutants show increased apoptosis accompanied by a loss of the distal progenitor markers Sftpc, Sox9 and Foxp2. In addition, Nubp1 mutation disrupts localization of the polarity protein Par3 and the mitosis relevant protein Numb. Using knock-down studies in lung epithelial cells, we also demonstrate a function of Nubp1 in regulating centrosome dynamics and microtubule organization. Together, Nubp1 represents an essential protein for lung progenitor survival by coordinating vital cellular processes including cell polarity and centrosomal dynamics.
authors.affiliation: Howard Hughes Medical Institute, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, United States of America.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schnatwinkel
authors.forename: Lee
authors.initials: L
authors.lastname: Niswander
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002386:Cataract / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D002470:Cell Survival; D018385:Centrosome / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D008171:Lung Diseases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016296:Mutagenesis; D017354:Point Mutation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013576:Syndactyly / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C400289:NUBP2 protein, mouse; C400290:Nubp1 protein, mouse; C115084:Pard3 protein, mouse; D019204:GTP-Binding Proteins