Sftpb

..The early expression of TTF-1 and HNF-3beta, preceding and overlapping that of pro-SP-B, mature SP-B, pro-SP-C, and CCSP, supports a regulatory role for TTF-1 and HNF-3beta in lung-specific gene expression...

..Direct and indirect transcriptional targets of TTF-1 were identified that are likely to play important roles in lung formation and function...

..The murine SP-B mRNA was expressed in proximal and distal epithelial cells within the respiratory tract and shares a close structural relationship to SP-B from other species...

..We propose a model in which Nmyc is essential in the developing lung for maintaining a distal population of undifferentiated, proliferating progenitor cells...

..Foxa2 regulates a complex pulmonary program of epithelial cell maturation required for transition to air breathing at birth...

..These observations establish, for the first time, both the sites and timing of specification of the proximal and peripheral airways in the developing lung, and that beta-catenin is one of the essential components of this specification...

..By contrast, Ptc is clearly upregulated in the transgenic lung. These results thus establish a role for SHH in lung morphogenesis, and suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo...

..Ectopic expression of HFH-4 in developing mouse lung altered epithelial cell differentiation and morphology, restricting the expression of markers typical of nonciliated cells of the distal lung parenchyma...

..These findings have implications for our understanding of the pathophysiology of ARDS and may guide future therapeutic strategies...

..Celsr3 and Fzd3 are expressed together during brain development and may act in synergy. Thus, a genetic pathway analogous to the one that controls PCP is key in the development of the axonal blueprint...

..These results suggest that the role of endogenous SP-B in host defense may be limited; however, synthetic peptides derived from SP-B may be useful in the treatment of bacterial pneumonias...

..Analysis of other family members demonstrated some overlapping embryonic expression of RAIG3 mRNA that could have led to functional redundancy in the single RAIG1 null mutant mouse...

..Foxa family members regulate signaling and transcriptional programs required for morphogenesis and cell differentiation during formation of the lung...

..Prop1-null mice are an excellent model for MPHD and may be useful for testing the efficacy of pharmaceutical intervention for neonatal respiratory distress...

..The full range of effects of this pathway, which includes the transcription factor Lef1, has not been explored, however...

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..We conclude that eNOS plays a previously unrecognized role in lung development, which may have relevance for clinical syndromes of neonatal respiratory distress...

..Although they have a number of biochemical and structural abnormalities, one cause of death is from apparent respiratory failure due to developmental pulmonary abnormalities...

..The alpha1,2-mannosidase IB null phenotype differs from phenotypes caused by ablation of other enzymes in N-glycan biosynthesis and from other mouse gene disruptions that affect pulmonary development and function...

..They also demonstrate the utility of the Abca3 null mouse as a model for a devastating human disease...

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..Therefore, we provide in vivo and in vitro evidence to demonstrate that Fstl1 modulates lung development and alveolar maturation, in part, through BMP4 signaling...

..This suggests a novel regulatory loop of Bmp4-Smad1-Wif1-Wnt/β-catenin in coordinating BMP and Wnt pathways to control fetal lung development...

..These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells...

..We conclude that pulmonary ErbB4 deletion results in a structural and functional delay in fetal lung development, indicating a crucial regulatory role of ErbB4 in the timely progression of fetal lung development...

..Thus, the signaling pathway by which TGFbeta/ALK5 regulates Clara cell differentiation may entail inhibition of Pten expression, which in turn activates ERK and AKT phosphorylation...

..The results suggest that NDST1-dependent HS is essential for proper functioning of BMP in embryonic lung development...

..our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb(-/-) mice, thereby inhibiting surface tension-lowering properties of surfactant in vivo within 24 hours after ..

..Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration...

..We propose that the Cited2-Tcfap2c complex controls lung maturation by regulating Cebpa expression. Understanding the function of this complex may provide novel therapeutic strategies for patients with respiratory distress syndromes...

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..Therefore, our data suggest that deficiency of appropriate BMP signaling in lung epithelial cells results in prenatal lung malformation, neonatal atelectasis, and respiratory failure...

..03). This study demonstrates for the first time a role for MIF in lung maturation, and supports a protective role for MIF in newborn lung disease...

..Collectively, these findings strongly suggest that ABCA3 is necessary for lamellar body biogenesis, surfactant protein-B processing, and lung development late in gestation...

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..These data demonstrate a critical role for PSR in early stages of mammalian organogenesis and suggest that this receptor may be involved in respiratory distress syndromes and congenital brain malformations...

..These defects lead to rupture of the major vessels and hemorrhage in the lungs after birth. These results demonstrate that Wnt7b signaling is required for proper lung mesenchymal growth and vascular development...

..These results suggest that elevated expression of SP-C(24-57)HA in type II cells resulted in aggregation of SP-C in the early secretory pathway, leading to cytotoxicity and, ultimately, altered lung development...

..These data suggest that gremlin plays an important role in lung morphogenesis by regulating the proximal-distal patterning of the lung during development...

..Fibroblast growth factor (FGF) 10 and FGF7 both decrease Foxf1 expression and we speculate that this is mediated by transcriptional activation of epithelial Bmp4 (in the case of FGF10) and by inhibition of Shh expression for FGF7...

..Since Dach1 mutants die shortly after birth, it remains possible that Dach1 is required for postnatal development of these structures. Alternatively, an additional Dach homologue may functionally compensate for Dach1 loss of function...

..In addition, a minor proportion of NDST-1-deficient embryos die during the embryonic period. The cause of the embryonic lethality is still obscure, but incompletely penetrant defects of the skull and the eyes have been observed...

..We conclude that these data suggest that mild prolonged fetal hypoxia produces alterations that could affect fetal cellular differentiation early in gestation and can induce changes consistent with lung maturation closer to term...

..Linkage and polymorphism analysis is explaining the role these genes may play in lung diseases and infection...

..These data support the concept that SP-B plays an important protective role in the lung...

..Combined with previous mapping studies, these data indicate that, with the possible exception of gamma1 and gamma11, the G protein gamma subunit genes are well dispersed within the mouse and human genomes...

..Thus, in the embryonic lung epithelium, growth effects of FGFs appear to be dependent on location of FGFRs, while effects on differentiation are ligand-dependent...

..TNF-alpha-mediated decrease in SP gene expression may contribute to the surfactant dysfunction and atelectasis observed in inflammatory lung diseases...

..Human chromosomes 2p13 and 10q25 have been involved in specific tumors where the role of Mad and Mxi1 can now be investigated...

..Ablation of the SP-B gene disrupts the routing, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth...

..Genetically decreased levels of SP-B combined with superimposed O(2)-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo...

..Our study demonstrates that Nfib is essential for normal lung development, and suggests that it could be involved in the pathogenesis of respiratory distress syndromes in humans...

..The studies support the concept that surfactant protein B homeostasis is influenced by neutral lipid metabolites in the lung...

..We also demonstrate localization of Netrin-1, DCC and UNC5H2 during the stages of lung development. We present evidence that these proteins are modulated spatially in the mesenchyme and epithelium during lung organogenesis...

..Together, results from QTL and microarray analyses of nickel-induced acute lung injury survival allowed us to generate a short list of candidate genes...

..Reduction of alveolar SP-B content causes surfactant dysfunction and respiratory failure, indicating that SP-B is required for postnatal lung function...

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..Overall, increased inflammation in SP-Bmon(+) mice was corrected to a large extent by increased gene dosage, indicating that formation of the intersubunit disulfide bridge is not critical for SP-B function...

..The temporal and spatial expression patterns of Sim2 in these skeletal elements suggest that Sim2 regulates their growth and/or integrity...

..Absence of WNT5a activity in the mutant lungs leads to increased expression of Fgf-10, Bmp4, Shh, and its receptor Ptc, raising the possibility that WNT5a, FGF-10, BMP4, and SHH signaling pathways are functionally interactive...

..Moreover, failure of this adaptive mechanism may increase pulmonary susceptibility to environmental insults, such as hypoxia and ischemia, ultimately leading to neonatal respiratory failure...

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..However, despite the ubiquitous presence of nidogens in basement membranes, defects do not occur in all tissues or in all basement membranes, suggesting a varying spectrum of roles for nidogens in the basement membrane...

..The mouse Sec13r gene was mapped to the conserved linkage group on chromosome 6 that corresponds to human chromosome 3p24-p25...

..The 5' flanking region of the murine SP-B contains cell-specific cis-active elements that regulate SP-B expression in the respiratory epithelium...

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..5-kb lacZ gene. The deletion abolished hSP-B lacZ gene expression in bronchiolar epithelial cells and significantly reduced its expression level in alveolar type II epithelial cells in transgenic mice...

..abstract_text> ..

..The potential opportunity to interfere with allergic sensitization by SP-D treatment bears high clinical significance. ..

..Finally, in order to help support the hypothesis that pro-apoptotic FasL activity characterized in human airway cells is truly physiologic, we will perform challenge studies in mice under FasL neutralizing conditions. ..

..The primary objective of this application is to set the stage for identifying the major gene(s) controlling survival by generating and testing genetically-refined mouse models containing susceptibility alleles in a fixed background. ..

..Furthermore, the molecular mechanisms, in particular the signaling pathways regulating Cebpa, of recombinant human FGF-7 treatment for acute lung injury will be determined. ..

..The primary objective of this application is to set the stage for identifying the major gene(s) controlling survival by generating and testing genetically-refined mouse models containing susceptibility alleles in a fixed background. ..

..The intended studies will provide fundamental insights into the role of SP-D in the protection of the lung, as well as into the basic mechanisms determining surfactant homeostasis. ..

..The goal is to understand the role of SP-D in the cellular and/or structural mechanisms involved in independent regulation of phospholipid and surfactant protein homeostasis. ..

..2. Elucidation of the cellular and molecular pathways of the glucocorticoid action on immune cell function and epithelial cell SP-D production in stress-induced exacerbation of the inflammatory airway response. ..