Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling

Scott, Ian C.; Blitz, Ira L.; Pappano, William N.; Maas, Sarah A.; Cho, Ken W. Y.; Greenspan, Daniel S.

doi:10.1038/35068572

Cited by 180 publications

(216 citation statements)

References 26 publications

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“…TSG orthologues have now been identified in various species, and in which they bind BMP4/DPP and Chordin/SOG in a ternary complex, and appear capable of either promoting or antagonizing BMP signaling in different in vivo contexts (Oelgeschlager et al, 2000;Chang et al, 2001;Ross et al, 2001;Scott et al, 2001). Although TSG does not appear to bind BMP1/ TLD-like proteinases, it does enhance the Chordinase activity of BMP1 and mTLL1 ).…”

Section: Twisted Gastrulation (Tsg)mentioning

confidence: 99%

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the activity necessary for proteolytic removal of the C-propeptides of procollagens I-III: precursors of the major fibrillar collagens. Subsequent studies have shown BMP1 to be the prototype of a small group of extracellular metalloproteinases that play manifold roles in regulating formation of the extracellular matrix (ECM). Soon after initial cloning of BMP1, genetic studies showed the related Drosophila proteinase Tolloid (TLD) to be necessary for formation of the dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD-like proteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of transforming growth factor β (TGFβ)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic (arthropods). More recently, it has become apparent that the BMP1/TLD-like proteinases are key activators of a broader subset of the TGFβ superfamily of proteins, with implications that these proteinases may be key in orchestrating formation of ECM with growth factor activation and BMP signaling in morphogenetic processes.

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Section: Twisted Gastrulation (Tsg)mentioning

confidence: 99%

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

2007

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“…For example, BMP1 and its Drosophila counterpart, Tolloid, unlike the other BMPs, are proteases that both function to cleave and thereby inactivate the BMP/Dpp antagonists chordin/sog (Marques et al, 1997;Blader et al, 1997;Goodman et al, 1998;Wardle et al, 1999). Twisted gastrulation is a direct-binding BMP antagonist/modulator that is also conserved between flies and vertebrates Chang et al, 2001;Ross et al, 2001;Scott et al, 2001). Thus, the dorsoventral antagonism of early Drosophila and Xe-nopus embryos is a sophisticated balancing of forces.…”

Section: Morphogens In Vivo Part Ii: Fgfs and Bmpsmentioning

confidence: 99%

Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment

Green

2002

Developmental Dynamics

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The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and ␤-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct longrange action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed.

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“…Tsg, which in Drosophila embryos specifies dorsal cell fate, has recently been shown to function as an extracellular BMP antagonist in vertebrates (17)(18)(19). Mouse Tsg can bind to and cleave Chordin, enhancing Chordin's ability to inhibit BMP4, and can also bind directly to BMP4 (19).…”

mentioning

confidence: 99%

“…Chordin also functions as a dorsalizing factor of the Xenopus Spemann organizer (15), and as a regulator of mammalian brain development (16). Tsg, which in Drosophila embryos specifies dorsal cell fate, has recently been shown to function as an extracellular BMP antagonist in vertebrates (17)(18)(19). Mouse Tsg can bind to and cleave Chordin, enhancing Chordin's ability to inhibit BMP4, and can also bind directly to BMP4 (19).…”

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confidence: 99%

Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation

Hager-Theodorides

Outram

Shah

et al. 2002

The Journal of Immunology

111

131

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Bone morphogenetic protein (BMP)2 and BMP4 are involved in the development of many tissues. In this study, we show that BMP2/4 signaling is involved in thymocyte development. Our data suggest that termination of BMP2/4 signaling is necessary for differentiation of CD44+CD25−CD4−CD8− double negative (DN) cells along the T cell lineage. BMP2 and BMP4 are produced by the thymic stroma and the requisite BMP receptor molecules (BMPR-1A, BMPR-1B, BMPR-II), and signal transduction molecules (Smad-1, -5, -8, and -4) are expressed by DN thymocytes. BMP4 inhibits thymocyte proliferation, enhances thymocyte survival, and arrests thymocyte differentiation at the CD44+CD25− DN stage, before T cell lineage commitment. Neutralization of endogenous BMP2 and BMP4 by treatment with the antagonist Noggin promotes and accelerates thymocyte differentiation, increasing the expression of CD2 and the proportion of CD44−CD25− DN cells and CD4+CD8+ double-positive cells. Our study suggests that the BMP2/4 pathway may function in thymic homeostasis by regulating T cell lineage commitment and differentiation.

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Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling

Cited by 180 publications

References 26 publications

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment

Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation

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