Talk:Developmental Signals - Bone Morphogenetic Protein
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Cite this page: Hill, M.A. (2024, April 19) Embryology Developmental Signals - Bone Morphogenetic Protein. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Developmental_Signals_-_Bone_Morphogenetic_Protein |
2013
Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18940-5. doi: 10.1073/pnas.1310479110. Epub 2013 Oct 16.
Yoshimatsu Y, Lee YG, Akatsu Y, Taguchi L, Suzuki HI, Cunha SI, Maruyama K, Suzuki Y, Yamazaki T, Katsura A, Oh SP, Zimmers TA, Lee SJ, Pietras K, Koh GY, Miyazono K, Watabe T. Author information
Abstract Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1 (ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation. KEYWORDS: angiogenesis, blood vascular endothelial cells, lymphangiogenesis
PMID 24133138
Bone morphogenetic proteins: The anomalous molecules
J Indian Soc Periodontol. 2013 Sep;17(5):583-586.
Jain AP, Pundir S, Sharma A. Author information
Abstract Bone is unique of all the tissues in the vertebrate organism. When injured, it heals by formation of new bone. Bone morphogenetic proteins (BMPs) are powerful inductors of the osteogenic activity during the embryologic bone formation phase and in cases of bone healing. They have proliferative effects on different cellular types, showing chemotactic properties and are able to induce mesenchymal cells differentiation into osteoblastic and chondroblastic line cells. Both primary cells and cell lines have been shown to respond to BMPs. Further the ability of embryonic cells to respond to BMPs by differentiating into cartilage and bone cells suggests that they are involved in the development of embryonic skeletal system. In addition, these proteins can also promote the angiogenesis, regulate the activity of some growth factors, and affect the production of these growth factors, which is helpful for the osteogenesis. BMPs have been considered as the most potent growth factors that can promote the bone regeneration. Thus, the aim of this review is to emphasize on the unique nature of the BMP molecules regarding their structure, classification, signaling mechanism, etc., as BMPs are the only molecules which show such deviation from the normal order, type. This will further help in understanding the role of BMPs and their potential advances which are necessary to facilitate the process of regeneration in periodontics. KEYWORDS: Bone, growth factors, healing, repair
PMID 24174749
2012
Opposing nodal and BMP signals regulate left-right asymmetry in the sea urchin larva
PLoS Biol. 2012;10(10):e1001402. doi: 10.1371/journal.pbio.1001402. Epub 2012 Oct 9.
Luo YJ, Su YH. Author information
Abstract
Nodal and BMP signals are important for establishing left-right (LR) asymmetry in vertebrates. In sea urchins, Nodal signaling prevents the formation of the rudiment on the right side. However, the opposing pathway to Nodal signaling during LR axis establishment is not clear. Here, we revealed that BMP signaling is activated in the left coelomic pouch, specifically in the veg2 lineage, but not in the small micromeres. By perturbing BMP activities, we demonstrated that BMP signaling is required for activating the expression of the left-sided genes and the formation of the left-sided structures. On the other hand, Nodal signals on the right side inhibit BMP signaling and control LR asymmetric separation and apoptosis of the small micromeres. Our findings show that BMP signaling is the positive signal for left-sided development in sea urchins, suggesting that the opposing roles of Nodal and BMP signals in establishing LR asymmetry are conserved in deuterostomes.
PMID 23055827
Anti-Mullerian hormone (AMH) is induced by bone morphogenetic protein (BMP) cytokines in human granulosa cells
Eur J Obstet Gynecol Reprod Biol. 2012 Jun 7. [Epub ahead of print]
Ogura-Nose S, Yoshino O, Osuga Y, Shi J, Hiroi H, Yano T, Taketani Y. Source Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan. Abstract OBJECTIVES: Serum concentration of anti-Mullerian hormone (AMH) is used as a biomarker in clinical practice. Therefore, it is important to elucidate the mechanism by which AMH is regulated in granulosa cells (GC). An important first step in understanding AMH regulation is to determine which factors up-regulate AMH expression. STUDY DESIGN: Human GC, obtained from 28 women undergoing oocyte retrieval for in vitro fertilization, were stimulated with various intraovarian cytokines including bone morphogenetic protein (BMP)-2, -6, -7 -15, activin-A and growth differentiation factor (GDF)-9 (100ng/ml). The expression of AMH mRNA was evaluated with reverse transcription and quantitative real-time polymerase chain reaction (PCR), and AMH protein in cultured supernatant was measured with EIA kit. RESULTS: BMP-2, -6, -7 and -15, but not activin-A and GDF-9, significantly induced AMH expression in GC at mRNA and protein level, while all stimuli increased FSH receptor mRNA and decreased steroidogenic acute regulatory protein (StAR) mRNA level. CONCLUSIONS: Among the transforming growth factor (TGF)-β superfamily, BMP-2, -6, -7 and -15 significantly induced AMH expression in human GC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
PMID 22682966
2011
SNW1 Is a Critical Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos
PLoS Biol. 2011 Feb 15;9(2):e1000593. doi: 10.1371/journal.pbio.1000593.
Wu MY, Ramel MC, Howell M, Hill CS.
Author information
Abstract Bone morphogenetic protein (BMP) gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate border formation and thus neural crest specification. Comment in SNW1 orchestrates BMP signaling in early embryonic patterning. [PLoS Biol. 2011]
PMID 21358802
http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000593
Developmental stalling and organ-autonomous regulation of morphogenesis
Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19270-5. Epub 2011 Nov 14.
Miletich I, Yu WY, Zhang R, Yang K, Caixeta de Andrade S, Pereira SF, Ohazama A, Mock OB, Buchner G, Sealby J, Webster Z, Zhao M, Bei M, Sharpe PT. Source Department of Craniofacial Development, Dental Institute, Kings College London, Guys Hospital, London SE1 6RT, United Kingdom.
Abstract
Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of Barx1 transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure.
PMID 22084104
2006
BMP and BMP inhibitors in bone
Ann N Y Acad Sci. 2006 Apr;1068:19-25.
Rosen V. Author information
Abstract Bone morphogenetic proteins (BMPs) are signaling molecules that act locally on target cells to affect cell survival, proliferation, and differentiation. While first identified as bone-inducing agents, BMPs are now known to affect the formation and function of many organ systems. Here we focus only on the roles of BMPs in the skeleton. In the developing mouse embryo, BMPs direct skeletal patterning, chondrogenesis, and bone formation. In postnatal animals, BMPs are potent bone regeneration factors, affecting both the amount of new bone formed and the rate at which bone healing occurs. The amount of BMP available for signaling is tightly regulated in both the embryo and postnatally, and in the context of the skeleton, several structurally distinct BMP ligand antagonists have been shown to alter the ability of BMPs to bind to their receptors, blocking BMP activity in physiologically important circumstances. For example, noggin knockout mice display cartilage hyperplasia during skeletal development that results in the loss of joint formation (too much BMP activity), while mice that overexpress noggin in skeletal cells display severe osteopenia and bone fragility (too little BMP activity). Sclerostin, chordin, CTGF, follistatin, and gremlin are additional BMP antagonists that may act in the skeleton to regulate BMP availability. Another class of BMP inhibitors are the proteins that bind to BMP receptors but have no inherent signaling function and thus act as BMP receptor antagonists. To date, inhibin and BMP-3 have been identified as BMP receptor antagonists that can block BMP signaling in bone. Identification of BMP antagonists allows us to investigate their role in diseases that affect skeletal function, such as osteopenia and nonunion fracture, and may provide a novel therapeutic intervention point for treatment. PMID 16831902
