Inhibition of branching morphogenesis and alteration of glycosaminoglycan biosynthesis in salivary glands treated with β-d-xyloside

Thompson, Holly; Spooner, Brian S.

doi:10.1016/0012-1606(82)90330-x

Cited by 84 publications

(31 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FGF10-FGFR2b signaling activates the MAPK cascade, regulating epithelial FGFR gene expression as well as the expression of ECM proteins in the basement membrane (Rebustini et al, 2007). HS is critical for SMG branching morphogenesis, as the addition of b-D-xyloside, bacterial heparitinase or exogenous heparin, inhibits ex vivo SMG branching (Mori, 1994;Nakanishi, 1993;Thompson and Spooner, 1982;Thompson and Spooner, 1983). Importantly, HS biosynthesis and accumulation in the basement membrane is coordinated with epithelial cell proliferation and end bud expansion.…”

Section: Introductionmentioning

confidence: 99%

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis

et al. 2007

View full text Add to dashboard Cite

Heparan sulfate proteoglycans are essential for biological processes regulated by fibroblast growth factors (FGFs). Heparan sulfate (HS) regulates the activity of FGFs by acting as a coreceptor at the cell surface, enhancing FGF-FGFR affinity, and being a storage reservoir for FGFs in the extracellular matrix (ECM). Here we demonstrate a critical role for heparanase during mouse submandibular gland (SMG) branching morphogenesis. Heparanase, an endoglycosidase, colocalized with perlecan in the basement membrane and in epithelial clefts of SMGs. Inhibition of heparanase activity in organ culture decreased branching morphogenesis, and this inhibition was rescued specifically by FGF10 and not by other FGFs. By contrast, exogenous heparanase increased SMG branching and MAPK signaling and, surprisingly, when isolated epithelia were cultured in a three-dimensional ECM with FGF10, it increased the number of lateral branches and end buds. In a solid-phase binding assay, an FGF10-FGFR2b complex was released from the ECM by heparanase. In addition, surface plasmon resonance (SPR) analysis showed that FGF10 and the FGF10-FGFR2b complex bound to purified perlecan HS and could be released by heparanase. We used the FGF10-FGFR2b complex as a probe for HS in SMGs, and it colocalized with perlecan in the basement membrane and partly colocalized with syndecan 1 in the epithelium, and binding was reduced by treatment with heparanase. In summary, our results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Increasing doses of the agent likely would not produce further changes in branching because the mechanism involved is a simple on-off switch. Examples of such a simple on-off effect on branching morphogenesis have been reported, in which once an effective dose was reached, increasing doses did not produce further large changes in bud formation (8,35,44,49). However, in the same system, the cell-specific expression of specific proteins, which are markers of stages in cell differentiation, might show more obvious progressive changes with increasing doses of the agent, as documented by our studies of expression of Hoxb5, Nkx2.1, and SP-C.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

Archavachotikul

Ciccone

Chinoy

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Although thyroid hormone (T3) influences epithelial cell differentiation during late fetal lung development, its effects on early lung morphogenesis are unknown. We hypothesized that T3 would alter embryonic lung airway branching and temporal-spatial differentiation of the lung epithelium and mesenchyme. Gestational day 11.5 embryonic mouse lungs were cultured for 72 h in BGJb serum-free medium without or with added T 3 (0.2, 2.0, 10.0, or 100 nM). Evaluation of terminal bud counts showed a dose-and time-dependent decrease in branching morphogenesis. Cell proliferation was also significantly decreased with higher doses of T 3. Morphometric analysis of lung histology showed that T 3 caused a dose-dependent decrease in mesenchyme and increase in cuboidal epithelia and airway space. Immunocytochemistry showed that with T 3 treatment, Nkx2.1 and surfactant protein SP-C proteins became progressively localized to cuboidal epithelial cells and mesenchymal expression of Hoxb5 was reduced, a pattern resembling late fetal lung development. We conclude that exogenous T 3 treatment during early lung development accelerated epithelial and mesenchymal cell differentiation at the expense of premature reduction in new branch formation and lung growth. triiodothyronine; lung development; Nkx2.1; Hoxb5; surfactant protein-C DURING FETAL DEVELOPMENT, lung morphology and differentiation of the airway lining epithelium change with advancing gestation. In the mouse, lung morphogenesis starts at gestational day 9.5 (Gd 9.5) with the evagination of the lung primordium from the ventral foregut to form the prospective trachea and two lung buds followed by the dichotomous branching of each lung bud through the process of branching morphogenesis. Differentiation of this lung primordium into the bronchial and pulmonary acinar systems begins during this period. The restriction of cell types and in some cases loss of cell-specific markers herald changes in the stage of bronchiolar versus distal epithelial cell fate and differentiation (48,58). These processes of airway branching and cytodifferentiation require a close interaction between endodermal epithelium and adjacent mesenchyme and are affected by specific factors and hormonal systems active in the developing embryo and fetus (1,22,24,35,38). In particular, in rodent lung organ cultures and human lung explant cultures, triiodothyronine (T 3 ), the active form of thyroid hormone, influences late fetal lung development by accelerating epithelial cell differentiation leading to surfactant phospholipid synthesis and by regulating lung structural development and alveolar septation (9,11,26,38). Little is known about the cellular expression pattern of T 3 receptors during fetal lung development, but they are present in rodent and human lung tissue during the pseudoglandular period and increase in quantity and binding affinity as lung development progresses (6,13,18,20,23). Although there are relatively low levels of T 3 and its receptors in early fetal life, maternal hypo-or hyperthyroidism le...

show abstract

“…The embryonic mouse submandibular mesenchyme has a rich ECM (20,1,5), and it might be expected that both the mesenchymal and epithelial cells of this and the other organs examined would have receptors for and would respond to the type I collagen and basement membrane components (Matrigel) used in this study. As these are such different substances they might be expected to exert different effects on organ development.…”

Section: Discussionmentioning

confidence: 99%

Growth and Morphogenesis of Embryonic Mouse Organs on Non‐Coated and Extracellular Matrix‐Coated Biopore Membrane

Hardman¹,

Klement

Spooner

1993

Dev Growth Differ

Self Cite

View full text Add to dashboard Cite

Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

show abstract

Inhibition of branching morphogenesis and alteration of glycosaminoglycan biosynthesis in salivary glands treated with β-d-xyloside

Cited by 84 publications

References 25 publications

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

Growth and Morphogenesis of Embryonic Mouse Organs on Non‐Coated and Extracellular Matrix‐Coated Biopore Membrane

Contact Info

Product

Resources

About