Mesenchyme specificity in rodent salivary gland development: the response of salivary epithelium to lung mesenchyme in vitro

Development ◽  
1974 ◽  
Vol 32 (2) ◽  
pp. 469-493
Author(s):  
Kirstie A. Lawson
Keyword(s):  
Mesenchymal Cell ◽  
Branching Morphogenesis ◽  
Mouse Lung ◽  
Tubular Epithelium ◽  
Rat Lung ◽  
Lung Epithelium ◽  
Millipore Filter ◽  
Cell Densities ◽  
Gland Development

Lung mesenchyme is able to support budding and cytodifferentiation of salivary epithelial rudiments in vitro. No difference in response was found between submandibular and parotid epithelium from mouse or rat. There are several further features of this result, which is contradictory to previous findings. (1) Lung mesenchyme is quantitatively less effective than submandibular mesenchyme for supporting submandibular morphogenesis. At least part of this difference is attributed to the inability of submandibular epithelium to replace lung epithelium in supporting the growth of lung mesenchyme. (2) Rat lung mesenchyme is quantitatively more effective than mouse lung mesenchyme when recombined with mouse submandibular epithelium. This may be at least partly due to mouse lung being more easily damaged by the procedures used. (3) Whereas the response of submandibular epithelium to submandibular mesenchyme is equally good on an agar or Millipore filter (MF) substratum, the response to lung mesenchyme is severely reduced or eliminated on MF. This difference is interpreted in terms of different mesenchymal cell densities necessary for submandibular or lung mesenchyme to support branching morphogenesis. Salivary buds formed in lung mesenchyme after 6 days are smaller and more closely packed than in salivary mesenchyme. In these heterotypic recombinates, the accumulation of amylase-resistant, PAS-positive material in the buds is initially accelerated and the tubular epithelium accumulates glycogen.

Stage specificity in the mesenchyme requirement of rodent lung epithelium in vitro: a matter of growth control?

Development ◽  
1983 ◽  
Vol 74 (1) ◽  
pp. 183-206
Author(s):  
Kirstie A. Lawson
Keyword(s):  
Cell Cycle ◽  
Bronchial Epithelium ◽  
Branching Morphogenesis ◽  
S Phase ◽  
Growth Fraction ◽  
Early Event ◽  
Rat Lung ◽  
Lung Epithelium ◽  
Dividing Cells

Epithelia from lung rudiments in which secondary bronchial buds are already established (14th and 13th gestational day for rat and mouse respectively) are able to undergo branching morphogenesis and cytodifferentiation in submandibular mesenchyme in vitro, whereas lung epithelium from one day younger foetuses rarely gives a morphogenetic response to submandibular mesenchyme and usually differentiates into primary (non-budding) bronchial epithelium. The failure of 13-day rat lung epithelium to respond to submandibular mesenchyme can be prevented by peeling off the submandibular mesenchyme from the lung epithelium after 2½ days culture and replacing the same mesenchyme, or renewing it with fresh salivary mesenchyme ex vivo. Changes in the epithelial contour are visible by 10 h and buds form within 24 h; this is followed by branching morphogenesis in more than 66% of the samples. The number of cells in S-phase in the epithelium is doubled within 3 to 5 h after the operation and the number of mitotic cells (colchicine block) is increased during an 11 to 19 h period after the operation. Substituting stomach mesenchyme for submandibular mesenchyme after the operation failed to elicit morphogenesis or an increase in the number of S-phase cells in the epithelium. The proportion of epithelial cells in S-phase in unoperated recombinates does not differ from the proportion in the primary bronchial epithelium (non-budding) of homotypic lung recombinates, whereas the proportion of S-phase cells in operated recombinates approaches that found in the buds of homotypic lung recombinates. The distribution of S-phase cells in visibly responding recombinates 15 to 17 h after operation shows the same heterogeneity as in homotypic lung recombinates, newly formed buds having twice as many cells labelled with [3H]thymidine as the non-budding area. Cell cycle parameters of intact rat lung growing in vitro were estimated using the labelled mitoses method. Primary bronchial epithelium and bronchial buds both had a total cell cycle time of about 13 h and an S-phase of about 10 h. The growth fraction was 0·54 in the primary bronchus and 0·95 in the buds. It is suggested that, also in the recombinates, differences in the proportion of S-phase cells at any one time in morphogenetically active and inactive areas of the epithelium are due to differences in the growth fraction. It is concluded that an early event in the morphogenetic response of lung epithelium to submandibular mesenchyme after removing and restoring the mesenchyme is an increase in the size of the population of dividing cells and it is suggested that a high proportion of dividing cells in an epithelial population is a prerequisite for further interaction of epithelium and mesenchyme leading to branching morphogenesis.

Mesenchymal control over elongating and branching morphogenesis in salivary gland development

Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 209-221
Author(s):  
Hiroyuki Nogawa ◽  
Takeo Mizuno
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Submaxillary Gland ◽  
Branching Morphogenesis ◽  
Mouse Submaxillary Gland ◽  
Gland Development

Recombination of the epithelium and mesenchyme between quail anterior submaxillary gland (elongating type) and quail anterior lingual or mouse submaxillary gland (branching type) was effected in vitro to clarify whether the elongating morphogenesis was directed by the epithelial or the mesenchymal component. Quail anterior submaxillary epithelium recombined with quail anterior lingual or mouse submaxillary mesenchyme came to branch. Conversely, quail anterior lingual or 12-day mouse submaxillary epithelium recombined with quail anterior submaxillary mesenchyme came to elongate, though the mesenchyme was less effective with 13-day mouse submaxillary epithelium. These results suggest that the elongating or branching morphogenesis of quail salivary glands is controlled by the mesenchyme.

Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium

1996 ◽  
Vol 271 (3) ◽  
pp. L392-L399 ◽  
Author(s):  
T. M. Nguyen ◽  
H. Guillozo ◽  
L. Marin ◽  
C. Tordet ◽  
S. Koite ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Mesenchymal Cell ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Alveolar Type ◽  
Target Tissue ◽  
Rat Lung ◽  
Lung Epithelium ◽  
Dihydroxyvitamin D3 ◽  
Developing Rat

Rat fetal lung is a target tissue for 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25 (OH)2 D3]. We have identified the cells that respond to the hormone and tested the hypothesis that the lung is also a source of 1 alpha,25(OH)2D3. We found that 1) at the end of pregnancy (days 20-21) alveolar type II cells (ATII) bore 1 alpha,25(OH)2D3 receptors and responded to the hormone. Incubating these cells with 10(-9) M 1 alpha,25(OH)2D3 for 48 h stimulated the synthesis (87.3 +/- 9.1%) and release (61.7 +/- 6.1%) of disaturated phosphatidylcholine; 2) EB-1213, a 1 alpha,25(OH)2D3 analogue with low calcemic activity, had similar effects on ATII; 3) neither fetal lung fibroblasts nor neonatal ATII (day 2 postpartum) expressed 1 alpha,25(OH)2D3 receptors; and 4) in contrast, fetal lung fibroblasts taken on days 19-22 of gestation converted [3H]25(OH)D3 to [3H]1 alpha,25(OH)2D3, whereas ATII and skin fibroblasts did not. These findings suggest that 1 alpha,25(OH)2D3 is a local mediator of epithelial-mesenchymal cell interactions in the developing rat lung and that 1 alpha,25(OH)2D3 or EB-1213 might be therapeutically useful in treating the respiratory distress syndrome of premature neonates.

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.

In vitro branching morphogenesis of the fetal rat lung

1993 ◽  
Vol 15 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Emad A. S. Massoud ◽  
Harmanjatinder S. Sekhon ◽  
Avi Rotschild ◽  
Martin L. Puterman ◽  
Reiko Matsui ◽  
...  
Keyword(s):  
Branching Morphogenesis ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

Epithelial and mesenchymal cell interactions with extracellular matrix material in vitro

Development ◽  
1969 ◽  
Vol 22 (3) ◽  
pp. 395-405
Author(s):  
H. C. Slavkin ◽  
P. Bringas ◽  
J. Cameron ◽  
R. LeBaron ◽  
L. A. Bavetta
Keyword(s):  
Matrix Material ◽  
Chorioallantoic Membrane ◽  
Tooth Germ ◽  
Mesenchymal Cell ◽  
Basic Rule ◽  
Millipore Filter ◽  
Chick Chorioallantoic Membrane ◽  
Mammalian Embryos ◽  
Tooth Germs

Epidermal organogenesis (thyroid gland, salivary gland, feather, hair, skin, thymus gland, tooth, etc.) generally follows a basic rule; epithelium exhibits well-documented interdependence with adjacent mesenchyme for a specific path of development (Grobstein, 1967, for review). Koch (1967) demonstrated in rodent embryos that isolates of incisor epithelial and mesenchymal tissue, separated by a millipore filter, continued to develop. When homotypic tissues were placed in juxtaposition to the filter, no evidence of continued differentiation was observed. Isolated cervical loop tissues of tooth germs from mammalian embryos have been shown to develop into an entire tooth in vitro (Slavkin & Bavetta, 1968 a; Kollar & Baird, 1969). Our laboratory recently reported that isolated tissue preparations (Slavkin & Bavetta, 1968 a) or cell suspensions (Slavkin, Beierle & Bavetta, 1968) of epithelial and mesenchymal cells from the embryonic cervical loop, in recombination on the chick chorioallantoic membrane (CAM), reconstituted and developed into a tooth germ.

MEK-1/2 inhibition reduces branching morphogenesis and causes mesenchymal cell apoptosis in fetal rat lungs

2002 ◽  
Vol 282 (3) ◽  
pp. L370-L378 ◽  
Author(s):  
David E. Kling ◽  
Hans K. Lorenzo ◽  
Alexander M. Trbovich ◽  
T. Bernard Kinane ◽  
Patricia K. Donahoe ◽  
...  
Keyword(s):  
Map Kinases ◽  
Mesenchymal Cell ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Fetal Lung Development ◽  
Mitogen Activated Protein ◽  
Upstream Kinase

The roles of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinases-1 and -2 (ERK-1/2) in fetal lung development have not been extensively characterized. To determine if ERK-1/2 signaling plays a role in fetal lung branching morphogenesis, U-0126, an inhibitor of the upstream kinase MAP ERK kinase (MEK), was added to fetal lung explants in vitro. Morphometry as measured by branching, area, perimeter, and complexity were significantly reduced in U-0126-treated lungs. At the same time, U-0126 treatment reduced ERK-1/2, slightly increased p38 kinase, but did not change c-Jun NH2-terminal kinase activities, indicating that U-0126 specifically inhibited the ERK-1/2 enzymes. These changes were associated with increased apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunofluorescent labeling of anti-active caspase-3 in the mesenchyme of explants after U-0126 treatment compared with the control. Mitosis characterized by immunolocalization of proliferating cell nuclear antigen was found predominantly in the epithelium and was reduced in U-0126-treated explants. Thus U-0126 causes specific inhibition of ERK-1/2 signaling, diminished branching morphogenesis, characterized by increased mesenchymal apoptosis, and decreased epithelial proliferation in fetal lung explants.

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