Angiogenesis and morphogenesis of murine fetal distal lung in an allograft model

2000 ◽  
Vol 278 (5) ◽  
pp. L1000-L1007 ◽  
Author(s):  
Margaret A. Schwarz ◽  
Fangrong Zhang ◽  
John E. Lane ◽  
Susan Schachtner ◽  
Yangsun Jin ◽  
...  
Keyword(s):  
Gestational Age ◽  
Lung Development ◽  
Surfactant Protein ◽  
Structural Features ◽  
Mouse Lung ◽  
Pharmacological Agents ◽  
Embryonic Mouse ◽  
Lung Morphogenesis ◽  
Distal Lung ◽  
Immunohistochemical Techniques

Neovascularization is crucial to lung morphogenesis; however, factors determining vessel growth and formation are poorly understood. The goal of our study was to develop an allograft model that would include maturation of the distal lung, thereby ultimately allowing us to study alveolar development, including microvascular formation. We transplanted 14-day gestational age embryonic mouse lung primordia subcutaneously into the back of nude mice for 3.5–14 days. Lung morphogenesis and neovascularization were evaluated by light microscopy, in situ hybridization, and immunohistochemical techniques. Embryonic 14-day gestational age control lungs had immature structural features consistent with pseudoglandular stage of lung development. In contrast, 14 days after subcutaneous transplantation of a 14-day gestational age lung, the allograft underwent significant structural morphogenesis and neovascularization. This was demonstrated by continued neovascularization and cellular differentiation, resulting in mature alveoli similar to those noted in the 2-day postnatal neonatal lung. Confirmation of maturation of the allograft was provided by progressive type II epithelial cell differentiation as evidenced by enhanced local expression of mRNA for surfactant protein C and a threefold ( P < 0.008) increase in vessel formation as determined by immunocytochemical detection of platelet endothelial cell adhesion molecule-1 expression. Using the tyrosine kinase Flk-1 receptor ( flk-1) LacZ transgene embryos, we determined that the neovascularization within the allograft was from the committed embryonic lung endothelium. Therefore, we have developed a defined murine allograft model that can be used to study distal lung development, including neovascularization. The model may be useful when used in conjunction with an altered genetic background (knockout or knock in) of the allograft and has the further decided advantage of bypassing placental barriers for introduction of pharmacological agents or DNA directly into the lung itself.

scholarly journals Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Marko Z Nikolić ◽  
Oriol Caritg ◽  
Quitz Jeng ◽  
Jo-Anne Johnson ◽  
Dawei Sun ◽  
...  
Keyword(s):  
Lung Development ◽  
Mouse Lung ◽  
Lung Epithelium ◽  
Human Embryonic Lung ◽  
Self Renewal ◽  
Embryonic Mouse ◽  
Multipotent Progenitors ◽  
Lung Epithelial

The embryonic mouse lung is a widely used substitute for human lung development. For example, attempts to differentiate human pluripotent stem cells to lung epithelium rely on passing through progenitor states that have only been described in mouse. The tip epithelium of the branching mouse lung is a multipotent progenitor pool that self-renews and produces differentiating descendants. We hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining morphology, gene expression and in vitro self-renewal and differentiation capacity of human tips. These experiments confirm that human and mouse tips are analogous and identify signalling pathways that are sufficient for long-term self-renewal of human tips as differentiation-competent organoids. Moreover, we identify mouse-human differences, including markers that define progenitor states and signalling requirements for long-term self-renewal. Our organoid system provides a genetically-tractable tool that will allow these human-specific features of lung development to be investigated.

Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4867-4878 ◽  
Author(s):  
S. Bellusci ◽  
J. Grindley ◽  
H. Emoto ◽  
N. Itoh ◽  
B.L. Hogan
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Lung Development ◽  
Expression Patterns ◽  
Branching Morphogenesis ◽  
Mouse Lung ◽  
Fibroblast Growth ◽  
Embryonic Mouse ◽  
Fibroblast Growth Factor 10

During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the mesenchyme adjacent to the distal buds from the earliest stages of lung development. The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm. In transgenic lungs overexpressing Shh in the endoderm, Fgf10 transcription is reduced, suggesting that high levels of SHH downregulate Fgf10. Addition of FGF10 to embryonic day 11.5 lung tissue (endoderm plus mesenchyme) in Matrigel or collagen gel culture elicits a cyst-like expansion of the endoderm after 24 hours. In Matrigel, but not collagen, this is followed by extensive budding after 48–60 hours. This response involves an increase in the rate of endodermal cell proliferation. The activity of FGF1, FGF7 and FGF10 was also tested directly on isolated endoderm in Matrigel culture. Under these conditions, FGF1 elicits immediate endodermal budding, while FGF7 and FGF10 initially induce expansion of the endoderm. However, within 24 hours, samples treated with FGF10 give rise to multiple buds, while FGF7-treated endoderm never progresses to bud formation, at all concentrations of factor tested. Although exogenous FGF1, FGF7 and FGF10 have overlapping activities in vitro, their in vivo expression patterns are quite distinct in relation to early branching events. We conclude that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.

scholarly journals Tumor necrosis factor-α and embryonic mouse lung morphogenesis

1994 ◽  
Vol 201 (2) ◽  
pp. 137-150 ◽  
Author(s):  
Tina Jaskoll ◽  
Paul D. Boyer ◽  
Michael Melnick
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mouse Lung ◽  
Embryonic Mouse ◽  
Lung Morphogenesis ◽  
Factor Α ◽  
Necrosis Factor

Lamellar body formation precedes pulmonary surfactant apoprotein expression during embryonic mouse lung development in vivo and in vitro

1989 ◽  
Vol 41 (3) ◽  
pp. 223-236 ◽  
Author(s):  
Harold C Slavkin ◽  
Peter Oliver ◽  
Pablo Bringas ◽  
Grace Don-Wheeler ◽  
Mark Mayo ◽  
...  
Keyword(s):  
Lung Development ◽  
Pulmonary Surfactant ◽  
Lamellar Body ◽  
Mouse Lung ◽  
Embryonic Mouse ◽  
Body Formation ◽  
Surfactant Apoprotein

Impact of embryonic Fgf10 expression deficiency on embryonic mouse lung development and hyperoxia lung injury

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
CM Chao ◽  
D Al Alam ◽  
R Schermuly ◽  
H Ehrhardt ◽  
KP Zimmer ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Development ◽  
Mouse Lung ◽  
Embryonic Mouse ◽  
Fgf10 Expression

Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis

1992 ◽  
Vol 149 (1) ◽  
pp. 123-133 ◽  
Author(s):  
David Warburton ◽  
Rajeev Seth ◽  
Lillian Shum ◽  
Philip G. Horcher ◽  
Frederick L. Hall ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mouse Lung ◽  
Embryonic Mouse ◽  
Lung Morphogenesis ◽  
Factor Expression ◽  
Epidermal Growth ◽  
Growth Factor Expression

IL-1β expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice

2014 ◽  
Vol 306 (1) ◽  
pp. L23-L34 ◽  
Author(s):  
Anna Hogmalm ◽  
Maija Bry ◽  
Birgitta Strandvik ◽  
Kristina Bry
Keyword(s):  
Respiratory Failure ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Secretory Protein ◽  
Clara Cell ◽  
Clara Cells ◽  
Lung Morphogenesis ◽  
Fetal Mice ◽  
Distal Lung ◽  
Cellular Area

Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1β in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1β under the control of the surfactant protein (SP)-C promoter. IL-1β-expressing pups suffered respiratory failure and died shortly after birth. IL-1β caused fetal lung inflammation and enhanced the expression of keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein 3 (MCP-3/CCL7), the calgranulins S100A8 and S100A9, the acute-phase protein serum amyloid A3, the chitinase-like proteins Ym1 and Ym2, and pendrin. IL-1β decreased the percentage of the total distal lung area made up of air saccules and the number of air saccules in the lungs of fetal mice. IL-1β inhibited the expression of VEGF-A and its receptors VEGFR-1 and VEGFR-2. The percentage of the cellular area of the distal lung made up of capillaries was decreased in IL-1β-expressing fetal mice. IL-1β suppressed the production of SP-B and pro-SP-C and decreased the amount of phosphatidylcholine and the percentage of palmitic acid in the phosphatidylcholine fraction of lung phospholipids, indicating that IL-1β prevented the differentiation of type II epithelial cells. The production of Clara cell secretory protein in the nonciliated bronchiolar (Clara) cells was likewise suppressed by IL-1β. In conclusion, expression of IL-1β in the epithelium of the distal airways disrupted the development of the airspaces and capillaries in the fetal lung and caused fatal respiratory failure at birth.

Glucuronyl C5-epimerase is crucial for epithelial cell maturation during embryonic lung development

Glycobiology ◽  
2020 ◽  
Author(s):  
Hao Cui ◽  
Xiaowen Cheng ◽  
Tahira Batool ◽  
Xiao Zhang ◽  
Jin-Ping Li
Keyword(s):  
Lung Development ◽  
Surfactant Protein ◽  
Branching Morphogenesis ◽  
Sulfated Polysaccharide ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Alveolar Epithelial ◽  
Neonatal Lethality ◽  
Key Enzyme ◽  
Distal Lung

Abstract Glucuronyl C5-epimerase (Hsepi) is a key enzyme in the biosynthesis of heparan sulfate that is a sulfated polysaccharide expressed on the cell surface and in the extracellular matrix of alveolar walls and blood vessels. Targeted interruption of the Hsepi gene, Glce, in mice resulted in neonatal lethality, which is most likely due to lung atelectasis. In this study, we examined the potential mechanisms behind the defect in lung development. Histological analysis of the lungs from embryos revealed no difference in the morphology between wild-type and mutant animals up to E16.5. This suggests that the initial events leading to formation of the lung primordium and branching morphogenesis are not disturbed. However, the distal lung of E17.5–18.5 mutants is still populated by epithelial tubules, lacking the typical saccular structural characteristic of a normal E17.5 lung. Immunostaining revealed strong signals of surfactant protein-C, but a weaker signal of T1α in the mutant lungs in comparison to WT littermates, suggesting differentiation of type I alveolar epithelial cells (AT1) is impaired. One of the parameters contributed to the failure of AT1 maturation is reduced vascularization in the developing lungs.

scholarly journals Retinoic acid and dexamethasone affect RAR-β and surfactant protein C mRNA in the MLE lung cell line

1998 ◽  
Vol 274 (1) ◽  
pp. L1-L7 ◽  
Author(s):  
Mary A. Grummer ◽  
Richard D. Zachman
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Lung Development ◽  
Actinomycin D ◽  
Surfactant Protein ◽  
Mouse Lung ◽  
Epithelial Cell Line ◽  
Surfactant Protein C ◽  
Lung Epithelial ◽  
Lung Cell Line

Lung development and surfactant biosynthesis are affected by retinoic acid (RA) and dexamethasone (Dex). Using a mouse lung epithelial cell line, we are exploring RA-Dex interactions through the study of RA and Dex effects on RA receptor (RAR) and surfactant protein (SP) C mRNA expression. RA increased expression of RAR-β (5.5 times) and SP-C (2 times) mRNA, with maximal effects at 24 h and at 10−6 M. The RA induction was not inhibited by cycloheximide, suggesting RA affects transcription. With added actinomycin D, RA did not affect the disappearance rate of RAR-β mRNA, but SP-C mRNA degradation was slowed, indicating an effect on SP-C mRNA stability. Dex decreased RAR-β and SP-C expression to 75 and 70% of control values, respectively, with greatest effects at 48 h and at 10−7 M. There was no effect of Dex on either RAR-β or SP-C mRNA disappearance with actinomycin D. However, cycloheximide prevented the effect of Dex. Despite Dex, RA increased both RAR-β and SP-C mRNA. This work suggests that RA and Dex affect RAR-β and SP-C genes by different mechanisms.

scholarly journals Evidence for the Involvement of theGliGene Family in Embryonic Mouse Lung Development

1997 ◽  
Vol 188 (2) ◽  
pp. 337-348 ◽  
Author(s):  
Justin C. Grindley ◽  
Savério Bellusci ◽  
Douglas Perkins ◽  
Brigid L.M. Hogan
Keyword(s):  
Lung Development ◽  
Mouse Lung ◽  
Embryonic Mouse
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