FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3615-3623 ◽  
Author(s):  
M. Weinstein ◽  
X. Xu ◽  
K. Ohyama ◽  
C.X. Deng
Keyword(s):  
Lung Development ◽  
Receptor Gene ◽  
Branching Morphogenesis ◽  
Fgf Receptor ◽  
Murine Lung ◽  
Targeted Mutation ◽  
Lung Abnormalities ◽  
Postnatal Lung Development ◽  
Receptor Gene Expression ◽  
Multiple Stages

Mammalian lungs begin as an outpocket of the foregut, and depend on multiple stages of branching morphogenesis and alveogenesis to reach their final form. An examination of fgf receptor gene expression indicated that all four receptors (fgfr-1 to fgfr-4) are expressed in postnatal lungs at varying levels. We show that mice homozygous for a targeted mutation of fgfr-4 exhibited no overt abnormalities in the lungs or any other organ. However, mice doubly homozygous for disruptions of the fgfr-3 and fgfr-4 genes display novel phenotypes not present in either single mutant, which include pronounced dwarfism and lung abnormalities. Lungs of fgfr-3(−/−)fgfr-4(−/−)animals, which are normal at birth, are completely blocked in alveogenesis and do not form secondary septae to delimit alveoli. Consequently, air spaces in the lung are expanded and no alveoli can be seen. The mutant lungs failed to downregulate postnatal elastin deposition despite their normal levels of surfactant expression and cell proliferation. These data revealed a cooperative function of FGFR-3 and FGFR-4 to promote the formation of alveoli during postnatal lung development.

Blood-Borne Macromolecule Induces FGF Receptor Gene Expression After Focal Ischemia

1994 ◽  
pp. 261-264
Author(s):  
Kazuo Yamada ◽  
T. Sakaguchi ◽  
T. Yuguchi ◽  
E. Kohmura ◽  
H. Otsuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Focal Ischemia ◽  
Fgf Receptor ◽  
Receptor Gene Expression

FGF receptor gene expression and its regulation by FGF signaling during early zebrafish development

genesis ◽  
2010 ◽  
Vol 48 (12) ◽  
pp. spcone-spcone
Author(s):  
Satoshi Ota ◽  
Noriko Tonou-Fujimori ◽  
Yukiko Nakayama ◽  
Yuki Ito ◽  
Akinori Kawamura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Fgf Signaling ◽  
Fgf Receptor ◽  
Zebrafish Development ◽  
Receptor Gene Expression

Iroquoisgenes influence proximo-distal morphogenesis during rat lung development

2006 ◽  
Vol 290 (4) ◽  
pp. L777-L789 ◽  
Author(s):  
Minke van Tuyl ◽  
Jason Liu ◽  
Freek Groenman ◽  
Ross Ridsdale ◽  
Robin N. N. Han ◽  
...  
Keyword(s):  
Lung Development ◽  
Cell Formation ◽  
Surfactant Protein ◽  
Branching Morphogenesis ◽  
Secretory Protein ◽  
Clara Cell ◽  
Fgf Receptor ◽  
Clara Cell Secretory Protein ◽  
Morphogenetic Protein

Lung development is a highly regulated process directed by mesenchymal-epithelial interactions, which coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. The Iroquois homeobox ( Irx) genes have been implicated in the patterning and specification of several Drosophila and vertebrate organs, including the heart. Herein, we investigated whether the Irx genes play a role in lung morphogenesis. We found that Irx1– 3 and Irx5 expression was confined to the branching lung epithelium, whereas Irx4 was not expressed in the developing lung. Antisense knockdown of all pulmonary Irx genes together dramatically decreased distal branching morphogenesis and increased distention of the proximal tubules in vitro, which was accompanied by a reduction in surfactant protein C-positive epithelial cells and an increase in β-tubulin IV and Clara cell secretory protein positive epithelial structures. Transmission electron microscopy confirmed the proximal phenotype of the epithelial structures. Furthermore, antisense Irx knockdown resulted in loss of lung mesenchyme and abnormal smooth muscle cell formation. Expression of fibroblast growth factors (FGF) 1, 7, and 10, FGF receptor 2, bone morphogenetic protein 4, and Sonic hedgehog (Shh) were not altered in lung explants treated with antisense Irx oligonucleotides. All four Irx genes were expressed in Shh- and Gli2-deficient murine lungs. Collectively, these results suggest that Irx genes are involved in the regulation of proximo-distal morphogenesis of the developing lung but are likely not linked to the FGF, BMP, or Shh signaling pathways.

Potential role of RGD-binding integrins in mammalian lung branching morphogenesis

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 551-558 ◽  
Author(s):  
J. Roman ◽  
C.W. Little ◽  
J.A. McDonald
Keyword(s):  
Lung Development ◽  
Branching Morphogenesis ◽  
Integrin Receptors ◽  
Murine Lung ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Mammalian Lung ◽  
Cell Matrix Interactions ◽  
Lung Branching

Cell-matrix interactions are generally considered critical for normal lung development. This is particularly likely to be true during the glandular stage, when the primitive airways are formed through a process termed branching morphogenesis. Integrins, transmembrane receptors that bind to extracellular matrices, are likely to mediate important interactions between embryonic cells and their matrices during branching morphogenesis. In this report, we examine the role of integrin receptors in this process. Immunohistochemical studies revealed that the integrins VLA 3, VLA 5 and integrin receptors to vitronectin are expressed in the epithelium and/or mesenchyme during the glandular stage of murine lung development. To correlate expression with function, an in vitro model of murine lung branching morphogenesis was utilized to examine branching in the presence of inhibitors of ligand binding to integrin receptors. One such reagent, a hexapeptide containing the RGD (Arg-Gly-Asp) sequence, diminished branching and resulted in an abnormal morphology, whereas a control peptide RGESP (Arg-Gly-Glu-Ser-Pro) had no effect. These findings suggest a critical role for cell-matrix interactions mediated via integrin receptors in early stages of mammalian lung development.

FGF receptor gene expression and its regulation by FGF signaling during early zebrafish development

genesis ◽  
2010 ◽  
Vol 48 (12) ◽  
pp. 707-716 ◽  
Author(s):  
Satoshi Ota ◽  
Noriko Tonou-Fujimori ◽  
Noriko Tonou-Fujimori ◽  
Yukiko Nakayama ◽  
Yuki Ito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Fgf Signaling ◽  
Fgf Receptor ◽  
Zebrafish Development ◽  
Receptor Gene Expression

Bombesin-like peptide receptor gene expression, regulation, and function in fetal murine lung

2004 ◽  
Vol 286 (1) ◽  
pp. L165-L173 ◽  
Author(s):  
Lin Shan ◽  
Rodica L. Emanuel ◽  
Denise Dewald ◽  
John S. Torday ◽  
Nithiananthan Asokanathan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Development ◽  
Gene Expression Regulation ◽  
Receptor Gene ◽  
Fetal Lung ◽  
Mouse Lung ◽  
Receptor Subtype ◽  
Fetal Lung Development ◽  
And Function ◽  
Receptor Gene Expression

Bombesin-peptide (BLP) immunoreactivity occurs at high levels in fetal lung. Previous studies showed that bombesin promotes fetal lung development. To test the hypothesis that such effects are mediated by known mammalian bombesin receptors [gastrin-releasing peptide (GRP)/bombesin-preferring receptor (GRPR), neuromedin B (NMB) receptor (NMBR), and the orphan bombesin receptor subtype-3 (BRS-3)], we analyzed the ontogeny of GRPR, NMBR, and BRS-3 gene expression in mouse lung. We examined the regulation of these three genes by dexamethasone and bombesin, which modulate lung development. Using incorporation of [3H]thymidine and [3H]choline, we then assessed whether GRP, NMB, and Leu8-phyllolitorin modulate lung growth and maturation in fetal lung explants. GRPR gene expression was detected predominantly in utero, whereas NMBR and BRS-3 genes were expressed from embryonic days 13–16 and on multiple postnatal days. All three mRNAs are present in airway epithelium and mesenchymal cells but occur in different relative patterns. These genes were regulated differently. Dexamethasone and bombesin increased GRPR mRNA, bombesin downregulated NMBR, and neither agent affected BRS-3. GRP increased incorporation of [3H]thymidine and [3H]choline in explants, whereas NMB induced cell proliferation and Leu8-phyllolitorin yielded variable results. Cumulative data suggest the involvement of multiple BLP receptors, including novel molecules, and argue against simple functional redundancy within this gene family during lung development.

Ectopic expression of C/EBPα in the lung epithelium disrupts late lung development

2006 ◽  
Vol 291 (4) ◽  
pp. L683-L693 ◽  
Author(s):  
Tove Berg ◽  
Lukas Didon ◽  
Magnus Nord
Keyword(s):  
Lung Development ◽  
Ectopic Expression ◽  
Surfactant Protein ◽  
Branching Morphogenesis ◽  
Developmental Expression ◽  
Lung Epithelium ◽  
Highly Active ◽  
Targeted Mutation ◽  
Differentiation And Proliferation ◽  
Pseudoglandular Stage

The lung develops from the endoderm through a process of branching morphogenesis. This process is highly active during the pseudoglandular stage of lung development and continues into the canalicular stage, resulting in the formation of terminal sacs. CCAAT/enhancer binding proteins (C/EBPs) are transcription factors regulating central aspects of differentiation and proliferation. We report here the developmental expression of C/EBPα, -β, and -δ in the lung. C/EBPα exhibits a dynamic expression pattern and is first detected during the late pseudoglandular stage. At this stage, expression is observed in a subset of epithelial cells in the distal parts of the branching tubules. The expression of C/EBPα is confined to nonproliferating cells. To examine the role of C/EBPα in lung development, we generated transgenic mice ectopically expressing C/EBPα in the lung epithelium using the human surfactant protein C promoter. Lungs from these mice were of normal size but exhibited a phenotype characterized by fewer and larger developing epithelial tubules, indicating that the branching process was affected. No effects on overall proliferation or cellular differentiation were observed. When this phenotype was compared with that of mice carrying a targeted mutation of the Cebpa gene, the Cebpa −/− mice exhibited a similar developmental phenotype. In conclusion, our results show a role for C/EBPα in lung development and suggest a function in the later stages of lung branching morphogenesis.

Hepatocyte growth factor (HGF) acts as a mesenchyme-derived morphogenic factor during fetal lung development

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1315-1324 ◽  
Author(s):  
H. Ohmichi ◽  
U. Koshimizu ◽  
K. Matsumoto ◽  
T. Nakamura
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Lung Development ◽  
Keratinocyte Growth Factor ◽  
Receptor Gene ◽  
Neutralizing Antibody ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Epithelial Tissue ◽  
Hepatocyte Growth

Mesenchymal-epithelial tissue interactions are important for development of various organs, and in many cases, soluble signaling molecules may be involved in this interaction. Hepatocyte growth factor (HGF) is a mesenchyme-derived factor which has mitogenic, motogenic and morphogenic activities on various types of epithelial cells and is considered to be a possible mediator of epithelial-mesenchymal interaction during organogenesis and organ regeneration. In this study, we examined the role of HGF during lung development. In situ hybridization analysis showed HGF and the c-met/HGF receptor gene to be respectively expressed in mesenchyme and epithelium in the developing lung. In organ cultures, exogenously added HGF apparently stimulated branching morphogenesis of the fetal lung. In contrast, HGF translation arrest or neutralization assays resulted in clear inhibition of epithelial branching. These results suggest that HGF is a putative candidate for a mesenchyme-derived morphogen regulating lung organogenesis. We also found that HGF is involved in epithelial branching, in collaboration with fibroblast growth factor (FGF) family molecule(s). In mesenchyme-free culture, HGF alone did not induce epithelial morphogenesis, however, addition of both HGF and acidic FGF (aFGF) or keratinocyte growth factor (KGF), ligands for the KGF receptor, induced epithelial branching more extensively than that was observed in explants treated with aFGF or KGF alone. In addition, the simultaneous inhibition of HGF- and FGF-mediated signaling using neutralizing antibody and antisense oligo-DNA resulted in drastic impairment of epithelial growth and branching. Possible interactions between HGF and FGFs or other growth factors in lung development is given consideration.

scholarly journals Tenascin-C deficiency impairs alveolarization and microvascular maturation during postnatal lung development

2020 ◽  
Vol 128 (5) ◽  
pp. 1287-1298 ◽  
Author(s):  
Sonja I. Mund ◽  
Johannes C. Schittny
Keyword(s):  
Lung Development ◽  
Matrix Protein ◽  
Branching Morphogenesis ◽  
Extracellular Matrix Protein ◽  
Wild Type ◽  
Tenascin C ◽  
Catch Up ◽  
Postnatal Lung Development ◽  
Alveolar Septa ◽  
Microvascular Maturation

Previously, we showed that the extracellular matrix protein tenascin-C takes part in prenatal lung development by controlling branching morphogenesis. Now we report that tenascin-C is also important during postnatal lung development, because tenascin-C deficiency delays the formation and maturation of the alveolar septa during not only classical but also continued alveolarization. Adult lungs are indistinguishable from wild type because of a catch-up formation of new septa.

VIRAL RECEPTOR GENE EXPRESSION AND MYOCARDITIS DEVELOPMENT

2016 ◽  
Vol 30 (1) ◽  
Author(s):  
A. Runov ◽  
◽  
E Kurchakova ◽  
D Khaschevskaya ◽  
O Moiseeva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Viral Receptor ◽  
Receptor Gene Expression
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