Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A)

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 833-844 ◽  
Author(s):  
K.M. Lyons ◽  
R.W. Pelton ◽  
B.L. Hogan
Keyword(s):  
Pattern Formation ◽  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Distribution Patterns ◽  
Tgf Beta ◽  
Atrioventricular Canal ◽  
Morphogenetic Protein ◽  
Hair Matrix

Bone morphogenetic protein-2A (BMP-2A) is a member of the transforming growth factor beta (TGF beta) gene family that has been implicated in cartilage and bone formation. Here we use in situ hybridization to show that BMP-2A RNA is expressed in a variety of embryonic epithelial and mesenchymal tissues outside of the developing skeletal system, including cell populations known to play important roles in morphogenesis. Thus, high levels of transcripts are found in developing limb buds (ventral ectoderm and apical ectodermal ridge), heart (myocardium of the atrioventricular canal), whisker follicles (ectodermal placodes, hair matrix and precortex cells), tooth buds (epithelial buds, dental papilla and odontoblasts), and craniofacial mesenchyme, as well as a number of other sites. The expression patterns of BMP-2A are different from those of TGF beta-1, -2 and -3, and this is illustrated in detail in the developing whisker follicles. These results suggest that BMP-2A plays multiple roles in morphogenesis and pattern formation in the vertebrate embryo.

scholarly journals mRNA expression of type I and type II receptors for activin, transforming growth factor-beta, and bone morphogenetic protein in the murine erythroleukemic cell line, F5-5.fl

2000 ◽  
pp. 705-710 ◽  
Author(s):  
H Machida ◽  
K Ogawa ◽  
M Funaba ◽  
T Mizutani ◽  
M Tsujimoto
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Morphogenetic Protein ◽  
Growth Factor Beta

OBJECTIVE: Intracellular signaling of activin and transforming growth factor-beta (TGF-beta) is thought to be mediated by the same molecules (Smad2/3 and Smad4). Although differentiation of murine erythroleukemia F5-5.fl cells is induced by activin, it is not induced by TGF-beta, suggesting that at some point TGF-beta signaling is defective. The aim of this study was to investigate the unresponsiveness of F5-5.fl cells to TGF-beta. DESIGN: mRNA expression of ligands, receptors, and signal mediators for the TGF-beta family was examined in F5-5.fl cells using RT-PCR. RESULTS: Activin induced erythrodifferentiation of F5-5.fl cells in a dose-dependent manner. Neither TGF-beta1 nor bone morphogenetic protein (BMP)-4 affected the differentiation of F5-5.fl cells in the presence or absence of activin. Although mRNAs of TGF-betas (TGF-beta1, TGF-beta2 and TGF-beta3) were detected, those of inhibin/activin (alpha-, betaA- and betaB-subunits) and BMPs (BMP-2, BMP-4 and BMP-7) could not be detected in the cells, suggesting that neither activins nor BMPs are produced in F5-5.fl cells. The expression of both type I (ALK-4/ActRIB) and type II (ActRII) receptors for activin was detected in F5-5.fl cells. In contrast, while the expression of type I receptor for TGF-beta (ALK-5/TbetaRI) was detected, that of type II receptor (TbetaRII) was not. The mRNA of all Smads examined was detected in F5-5.fl cells. CONCLUSIONS: A defect in the type II receptor might cause unresponsiveness to TGF-beta in F5-5.fl cells. An erythrodifferentiation assay using F5-5.fl cells would be useful for measuring net activin activity because it would not be necessary to consider endogenous activins and BMPs.

175. THE ROLE OF PROPROTEIN CONVERTASE 6 DURING DECIDUALIZATION: REGULATION OF BONE MORPHOGENETIC PROTEIN 2 ACTIVATION

2009 ◽  
Vol 21 (9) ◽  
pp. 93
Author(s):  
S. Heng ◽  
B. Hardman ◽  
S. Paule ◽  
H. Singh ◽  
G. Nie
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Active Form ◽  
Bone Morphogenetic Protein 2 ◽  
Tgf Beta ◽  
Proprotein Convertase ◽  
Morphogenetic Protein ◽  
Total Inhibition

Proprotein convertase 5/6 (PC6), a member of the proprotein convertase (PC) family, is a critical endometrial factor for implantation. PC6 is up-regulated in the endometrium specifically at implantation in association with epithelial differentiation (in human and monkey) and stromal cell decidualization (in the mouse, human and monkey). PC6 is the only PC member that was significantly up-regulated during decidualization. Knockdown of PC6 inhibits decidualization. PCs function by converting a range of important precursor proteins into their bioactive forms. One group of such proteins is the transforming growth factor beta (TGF-beta) superfamily proteins. They are first synthesized as larger biologically inactive precursors, and then are processed by PCs into their active forms. Bone morphogenetic protein 2 (BMP2) is a TGF-beta superfamily member and demonstrated to be essential for decidualization. We hypothesized that BMP2 is one of the proteins that PC6 activates during decidualization. Freshly isolated stromal cells from human endometrium were decidualized in culture with and without inhibition of PC6 activity. The full-length (precursor, non-active) and processed (activated) forms of BMP2 were determined in cellular lysates and media. The precursor form of BMP2 was reduced whereas the active form was increased during decidualization. Inhibition of PC6 activity inhibited decidualization, and this inhibition was accompanied by a total inhibition of the production of active BMP2. To further confirm the role of PC6 in activating BMP2 in decidualization, active BMP2 was added into cells and the decidualization arrest caused by PC6 inhibition was partially rescued. This study demonstrated that PC6 regulates decidualization by activating molecules such as BMP2 that are essential for decidualization.

scholarly journals Endothelial BMPR2 Loss Drives a Proliferative Response to BMP (Bone Morphogenetic Protein) 9 via Prolonged Canonical Signaling

2020 ◽  
Vol 40 (11) ◽  
pp. 2605-2618
Author(s):  
Anne L. Theilmann ◽  
Lindsey G. Hawke ◽  
L. Rhiannon Hilton ◽  
Mara K.M. Whitford ◽  
Devon V. Cole ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Morphogenetic Protein ◽  
Pulmonary Arterial ◽  
The Impact

Objective: Pulmonary arterial hypertension is a disease of proliferative vascular occlusion that is strongly linked to mutations in BMPR2 —the gene encoding the BMPR-II (BMP [bone morphogenetic protein] type II receptor). The endothelial-selective BMPR-II ligand, BMP9, reverses disease in animal models of pulmonary arterial hypertension and suppresses the proliferation of healthy endothelial cells. However, the impact of BMPR2 loss on the antiproliferative actions of BMP9 has yet to be assessed. Approach and Results: BMP9 suppressed proliferation in blood outgrowth endothelial cells from healthy control subjects but increased proliferation in blood outgrowth endothelial cells from pulmonary arterial hypertension patients with BMPR2 mutations. This shift from growth suppression to enhanced proliferation was recapitulated in control human pulmonary artery endothelial cells following siRNA-mediated BMPR2 silencing, as well as in mouse pulmonary endothelial cells isolated from endothelial-conditional Bmpr2 knockout mice ( Bmpr2 EC −/− ). BMP9-induced proliferation was not attributable to altered metabolic activity or elevated TGFβ (transforming growth factor beta) signaling but was linked to the prolonged induction of the canonical BMP target ID1 in the context of BMPR2 loss. In vivo, daily BMP9 administration to neonatal mice impaired both retinal and lung vascular patterning in control mice ( Bmpr2 EC+/+ ) but had no measurable effect on mice bearing a heterozygous endothelial Bmpr2 deletion ( Bmpr2 EC +/− ) and caused excessive angiogenesis in both vascular beds for Bmpr2 EC −/− mice. Conclusions: BMPR2 loss reverses the endothelial response to BMP9, causing enhanced proliferation. This finding has potential implications for the proposed translation of BMP9 as a treatment for pulmonary arterial hypertension and suggests the need for focused patient selection in clinical trials.

dally, a Drosophila glypican, controls cellular responses to the TGF-beta-related morphogen, Dpp

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4113-4120 ◽  
Author(s):  
S.M. Jackson ◽  
H. Nakato ◽  
M. Sugiura ◽  
A. Jannuzi ◽  
R. Oakes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ectopic Expression ◽  
Cellular Responses ◽  
Growth Factor Signaling ◽  
Tgf Beta ◽  
Morphogenetic Protein

Decapentaplegic (Dpp) is a Drosophila member of the Transforming Growth Factor-beta (TGF-beta)/Bone Morphogenetic Protein (BMP) superfamily of growth factors. Dpp serves as a classical morphogen, where concentration gradients of this secreted factor control patterning over many cell dimensions. Regulating the level of Dpp signaling is therefore critical to its function during development. One type of molecule proposed to modulate growth factor signaling at the cell surface are integral membrane proteoglycans. We show here that division abnormally delayed (dally), a Drosophila member of the glypican family of integral membrane proteoglycans is required for normal Dpp signaling during development, affecting cellular responses to this morphogen. Ectopic expression of dally+ can alter the patterning activity of Dpp, suggesting a role for dally+ in modulating Dpp signaling strength. These findings support a role for members of the glypican family in controlling TGF-beta/BMP activity in vivo by affecting signaling at the cell surface.

scholarly journals Regulatory Role of miRNA-375 in Expression of BMP15/GDF9 Receptors and its Effect on Proliferation and Apoptosis of Bovine Cumulus Cells

2017 ◽  
Vol 41 (2) ◽  
pp. 439-450 ◽  
Author(s):  
Hongyan Chen ◽  
Chang Liu ◽  
Hao Jiang ◽  
Yan Gao ◽  
Mingqiang Xu ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cumulus Cells ◽  
Apoptosis Rate ◽  
Morphogenetic Protein ◽  
Proliferation And Apoptosis ◽  
Growth Differentiation Factor 9 ◽  
Two Factors ◽  
Proliferation Ability

Background: Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are members of the transforming growth factor beta (TGF-β) superfamily. Through autocrine and paracrine mechanisms, these two factors can regulate cell differentiation, proliferation, and other functions in the ovary locally. Furthermore, GDF9 and BMP15 play vital roles in follicular growth, atresia, ovulation, fertilization, reproduction, and maintenance. Numerous studies have demonstrated a synergy between BMP15 and GDF9. Studies in humans and mice have indicated that the synergy between BMP15 and GDF9 is primarily mediated by the bone morphogenetic protein type II receptor (BMPR2). The BMP15/GDF9 heterodimer needs to bind to the BMPR2-ALK4/5/7-ALK6 receptor complex to activate the SMAD2/3 signaling pathway. However, it is not clear which genes mediate and regulate the effects of the BMP15/GDF9 proteins on bovine cumulus cells (CCs). Methods: Our earlier study showed that BMPR2 is a gene that is directly targeted and regulated by miR-375. Therefore, we designed and synthesized an miR-375 mimics/inhibitor and regulated BMPR2 expression in bovine CCs by the overexpression or inhibition of miR-375. After the overexpression or inhibition of miR-375, the apoptosis rate of bovine CCs was measured by flow cytometry; changes in critical gene expression were measured by RT-qPCR and western blot assays; and the proliferation of bovine CCs was measured by CCK-8 assay. Results: In bovine CCs, the overexpression of miR-375 resulted in decreased BMPR2 and ALK7 expression, whereas the inhibition of miR-375 caused increased BMPR2 and ALK7 expression. The overexpression of miR-375 attenuated the proliferation ability and significantly increased the apoptosis rate of bovine CCs, whereas the inhibition of miR-375 did not significantly change the proliferation ability or apoptosis rate. Conclusions: BMPR2, a target of miR-375, is regulated by this molecule, thereby affecting expression of BMP15/GDF9 receptors, and the proliferation and apoptosis of bovine CCs.

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