Developmental Signals - Bone Morphogenetic Protein
|Embryology - 26 Apr 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Structure
- 4 Function
- 5 Signaling Pathway
- 6 Additional Images
- 7 OMIM
- 8 References
- 9 External Links
- 10 Glossary Links
Belongs to the transforming growth factor-beta (TGFB) superfamily. The proteins are synthesized as prepropeptides, then cleaved, and then processed into dimeric proteins.
- TGFB family members: TGFB1, TGFB, TGFB3, bone morphogenetic proteins Bmp-2A, Bmp-2B, Bmp-3, and Bmp-6. mullerian inhibitory substance.
Mouse Bmp4 expression face.
- BMP Mouse Links: Face and limb E9.5-13.5 | Face E9.5-13.5 | Body E11.0 | Body E11.5 | BMP | Mouse Development
Growth Differentiation Factor-6 (Gdf6) is a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules.
|Factor Links: hCG | BMP | Sonic hedgehog | HOX | FGF | Nanog | Notch | FOX | PAX | Retinoic acid | SIX | Slit2/Robo1 | Sox | TBX | TGF-beta | VEGF | WNT | Hippo | Category:Molecular|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Mehran Zarei-Ghanavati, Venkata Avadhanam, Alfonso Vasquez Perez, Christopher Liu The osteo-odonto-keratoprosthesis. Curr Opin Ophthalmol: 2017; PubMed 28441214
Marcelina Koćwin, Mateusz Jonakowski, Marcelina Przemęcka, Michał Panek, Piotr Kuna Selected bone morphogenetic proteins - the possibility of their use in the diagnostics and therapy of severe asthma. Adv Respir Med: 2017, 85(2);109-115 PubMed 28440536
Kaisaier Aji, Yun Zhang, Abudusaimi Aimaiti, Yujie Wang, Mulati Rexiati, Baihetiya Azhati, Hamulati Tusong, Lei Cui, Chen Wang MicroRNA-145 regulates the differentiation of human adipose-derived stem cells to smooth muscle cells via targeting Krüppel-like factor 4. Mol Med Rep: 2017; PubMed 28440409
Tsuyoshi Sato, Shoichiro Kokabu, Yuichiro Enoki, Naoki Hayashi, Masahito Matsumoto, Mitsuhiko Nakahira, Masashi Sugasawa, Tetsuya Yoda Functional Roles of Netrin-1 in Osteoblast Differentiation. In Vivo: 2017, 31(3);321-328 PubMed 28438858
Yohei Kanamori, Masaru Murakami, Makoto Sugiyama, Osamu Hashimoto, Tohru Matsui, Masayuki Funaba IL-1β transcriptionally activates hepcidin by inducing C/EBPδ expression in hepatocytes. J. Biol. Chem.: 2017; PubMed 28438835
|BMP Superfamily Canonical Signalling|
| Over 30 bone morphogenetic protein (BMP) superfamily ligands have been discovered in humans. Most are secreted as mature disulfide-linked dimers, with the exception of TGF-β1, TGF-β2 and TGF-β3, which can be secreted in a latent form and require proteolytic activation. BMPs signal through a multimeric cell surface complex consisting of two type I receptors and two type II receptors.
Activated type I receptors recruit and phosphorylate pathway-specific R-SMADs (SMAD1, SMAD5 and SMAD8 (blue pathway), and SMAD2 and SMAD3 (orange pathway)), which can form trimers with SMAD4 and translocate to the nucleus. SMADs have intrinsic DNA-binding activity and are able to regulate gene expression by recruitment of chromatin-remodelling machinery and integration with tissue-specific transcription factors. SMAD8 is also known as SMAD9.
The pathway can be antagonized by many mechanisms including neutralization of ligands by secreted traps such as noggin or follistatin, secretion of latent ligands bound to their propeptides, or via titration of receptors by nonsignalling ligands such as BMP3, activin β/inhibin α dimers or LEFTY monomers.
Mouse Bmp4 expression limb and face.
During gastrulation the BMP pathway is antagonised and involved with neural induction. Neural induction signaling through the BMP-regulated Smad1/5 proteins appears to be controlled by fibroblast growth factor (FGF)-regulated Ca2+ entry activating calcineurin (CaN) that in turn dephosphorylates Smad1/5 proteins.
- Links: Neural Development
|Molecular paracrine interactions involving BMP15 signaling||Localization of BMP15 in calf and cow follicles|
- Links: Oocyte Development
Bmp2, Bmp4 and Bmp7 are co-required in the mouse AER for normal digit patterning but not limb outgrowth
- "Outgrowth and patterning of the vertebrate limb requires a functional apical ectodermal ridge (AER). The AER is a thickening of ectodermal tissue located at the distal end of the limb bud. Loss of this structure, either through genetic or physical manipulations results in truncation of the limb. A number of genes, including Bmps, are expressed in the AER. Previously, it was shown that removal of the BMP receptor Bmpr1a specifically from the AER resulted in complete loss of hindlimbs suggesting that Bmp signaling in the AER is required for limb outgrowth. In this report, we genetically removed the three known AER-expressed Bmp ligands, Bmp2, Bmp4 and Bmp7 from the AER of the limb bud using floxed conditional alleles and the Msx2-cre allele. Surprisingly, only defects in digit patterning and not limb outgrowth were observed. In triple mutants, the anterior and posterior AER was present but loss of the central region of the AER was observed. These data suggest that Bmp ligands expressed in the AER are not required for limb outgrowth but instead play an essential role in maintaining the AER and patterning vertebrate digits."
- Links: Limb Development
Blood Vessel Development
BMP/SMAD signaling pathway regulates angiogenic sprouting and is involved in embryo vascular development.
Identified BMP modulators: Noggin, Chordin, Chordin-like 1, Chordin-like 2, Twisted gastrulation, Dan, BMPER, Sost, Sostdc1, Follistatin, Follistatin-like 1, Follistatin-like 5 and Tolloid.
SNW-domain containing protein 1
(SNW1, SKI-INTERACTING PROTEIN; SKIIP)
A protein that interacts with nuclear receptors and enhances ligand-activated transcription, also called a nuclear receptor co-activator.
Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos
- "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."
About OMIM "Online Mendelian Inheritance in Man OMIM is a comprehensive, authoritative, and timely compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources." OMIM
- Links: OMIM300247
- 22701669</pubmed>| PLoS One
- Sumiyo Mimura, Mika Suga, Kaori Okada, Masaki Kinehara, Hiroki Nikawa, Miho K Furue Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells. Int. J. Dev. Biol.: 2016; PubMed 26934293
- Ethan Bier, Edward M De Robertis EMBRYO DEVELOPMENT. BMP gradients: A paradigm for morphogen-mediated developmental patterning. Science: 2015, 348(6242);aaa5838 PubMed 26113727
- Peng-Fei Xu, Nathalie Houssin, Karine F Ferri-Lagneau, Bernard Thisse, Christine Thisse Construction of a vertebrate embryo from two opposing morphogen gradients. Science: 2014, 344(6179);87-9 PubMed 24700857
- Isabelle Miletich, Wei-Yuan Yu, Ruofang Zhang, Kai Yang, Simone Caixeta de Andrade, Silvia Fontes do A Pereira, Atsushi Ohazama, Orin B Mock, Georg Buchner, Jane Sealby, Zoe Webster, Minglian Zhao, Marianna Bei, Paul T Sharpe Developmental stalling and organ-autonomous regulation of morphogenesis. Proc. Natl. Acad. Sci. U.S.A.: 2011, 108(48);19270-5 PubMed 22084104
- Valerie S Salazar, Laura W Gamer, Vicki Rosen BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol: 2016; PubMed 26893264
- Ahryon Cho, Yitai Tang, Jonathan Davila, Suhua Deng, Lei Chen, Erik Miller, Marius Wernig, Isabella A Graef Calcineurin signaling regulates neural induction through antagonizing the BMP pathway. Neuron: 2014, 82(1);109-24 PubMed 24698271
- Ewa Chronowska High-throughput analysis of ovarian granulosa cell transcriptome. Biomed Res Int: 2014, 2014;213570 PubMed 24711992 | PMC3966335 | Biomed Res Int.
- | PLoS One.
- Carlos I Lorda-Diez, Juan A Montero, Joaquin Rodriguez-Leon, Juan A Garcia-Porrero, Juan M Hurle Expression and functional study of extracellular BMP antagonists during the morphogenesis of the digits and their associated connective tissues. PLoS ONE: 2013, 8(4);e60423 PubMed 23573253
- Mary Y Wu, Marie-Christine Ramel, Michael Howell, Caroline S Hill SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos. PLoS Biol.: 2011, 9(2);e1000593 PubMed 21358802
Aena Pundir Jain, Siddharth Pundir, Anamika Sharma Bone morphogenetic proteins: The anomalous molecules. J Indian Soc Periodontol: 2013, 17(5);583-6 PubMed 24174749
Karen Ruschke, Christian Hiepen, Jessica Becker, Petra Knaus BMPs are mediators in tissue crosstalk of the regenerating musculoskeletal system. Cell Tissue Res.: 2012, 347(3);521-44 PubMed 22327483
Elisabetta Gazzerro, Ernesto Canalis Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord: 2006, 7(1-2);51-65 PubMed 17029022
Di Chen, Ming Zhao, Gregory R Mundy Bone morphogenetic proteins. Growth Factors: 2004, 22(4);233-41 PubMed 15621726
Ahryon Cho, Yitai Tang, Jonathan Davila, Suhua Deng, Lei Chen, Erik Miller, Marius Wernig, Isabella A Graef Calcineurin signaling regulates neural induction through antagonizing the BMP pathway. Neuron: 2014, 82(1);109-24 PubMed 24698271
Yi-Jyun Luo, Yi-Hsien Su Opposing nodal and BMP signals regulate left-right asymmetry in the sea urchin larva. PLoS Biol.: 2012, 10(10);e1001402 PubMed 23055827
Elke Kuypers, Jennifer J P Collins, Reint K Jellema, Tim G A M Wolfs, Matthew W Kemp, Ilias Nitsos, J Jane Pillow, Graeme R Polglase, John P Newnham, Wilfred T V Germeraad, Suhas G Kallapur, Alan H Jobe, Boris W Kramer Ovine fetal thymus response to lipopolysaccharide-induced chorioamnionitis and antenatal corticosteroids. PLoS ONE: 2012, 7(5);e38257 PubMed 22693607
- Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al.New York: Garland Science; 2002. Signal Proteins of the TGF-β Superfamily Act Through Receptor Serine/Threonine Kinases and Smads
- Madame Curie Bioscience Database (Internet). Austin (TX): Landes Bioscience; 2000. TGFβ-dependent Epithelial-Mesenchymal Transition
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- NCBI - Mouse BMP4 gene
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Cite this page: Hill, M.A. 2017 Embryology Developmental Signals - Bone Morphogenetic Protein. Retrieved April 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Bone_Morphogenetic_Protein
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G