Gene Symbol: Twsg1
Description: twisted gastrulation BMP signaling modulator 1
Alias: 1810013J15Rik, 9030422N06Rik, AW552143, D17Ertd403e, Tsg, Twg, twisted gastrulation protein homolog 1, twisted gastrulation homolog 1
Species: mouse
Products:     Twsg1

Top Publications

  1. Sun M, Forsman C, Sergi C, Gopalakrishnan R, O Connor M, Petryk A. The expression of twisted gastrulation in postnatal mouse brain and functional implications. Neuroscience. 2010;169:920-31 pubmed publisher
    Twisted gastrulation (TWSG1), an extracellular regulator of bone morphogenetic protein (BMP) signaling, is critical for embryonic brain development...
  2. Ikeya M, Fukushima K, Kawada M, Onishi S, Furuta Y, Yonemura S, et al. Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors. Dev Biol. 2010;337:405-14 pubmed publisher
    ..the renal defects of the Cv2(-/-) mutant were totally suppressed by a null mutation of Twisted gastrulation (Tsg), which encodes another BMP-binding factor, showing that Cv2 exerts its pro-BMP nephrogenic function Tsg-..
  3. Petryk A, Shimmi O, Jia X, Carlson A, Tervonen L, Jarcho M, et al. Twisted gastrulation and chordin inhibit differentiation and mineralization in MC3T3-E1 osteoblast-like cells. Bone. 2005;36:617-26 pubmed
    ..accessibility of BMP ligands for binding to their receptors is regulated by secreted proteins Twisted gastrulation (Tsg) and Chordin (Chd)...
  4. Nosaka T, Morita S, Kitamura H, Nakajima H, Shibata F, Morikawa Y, et al. Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. Mol Cell Biol. 2003;23:2969-80 pubmed
    Dorsoventral patterning depends on the local concentrations of the morphogens. Twisted gastrulation (TSG) regulates the extracellular availability of a mesoderm inducer, bone morphogenetic protein 4 (BMP-4)...
  5. Scott I, Blitz I, Pappano W, Maas S, Cho K, Greenspan D. Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling. Nature. 2001;410:475-8 pubmed
    Twisted gastrulation (TSG) is involved in specifying the dorsal-most cell fate in Drosophila embryos, but its mechanism of action is poorly understood...
  6. Passa O, Tsalavos S, Belyaev N, Petryk A, Potocnik A, Graf D. Compartmentalization of bone morphogenetic proteins and their antagonists in lymphoid progenitors and supporting microenvironments and functional implications. Immunology. 2011;134:349-59 pubmed publisher
    ..Bmp4, Bmp7, Gremlin and Twisted gastrulation (Twsg1) are all expressed in the thymus and expression was clearly different for each gene investigated...
  7. Sotillo Rodriguez J, Mansky K, Jensen E, Carlson A, Schwarz T, Pham L, et al. Enhanced osteoclastogenesis causes osteopenia in twisted gastrulation-deficient mice through increased BMP signaling. J Bone Miner Res. 2009;24:1917-26 pubmed publisher
    ..has been shown in various contexts to be regulated by extracellular proteins, including Twisted gastrulation (TWSG1). However, experimental paradigms determining the effects of BMP regulators on bone remodeling are limited...
  8. Billington C, Ng B, Forsman C, Schmidt B, Bagchi A, Symer D, et al. The molecular and cellular basis of variable craniofacial phenotypes and their genetic rescue in Twisted gastrulation mutant mice. Dev Biol. 2011;355:21-31 pubmed publisher
    ..Mice deficient in Twisted gastrulation (Twsg1(-/-)) display such phenotypic variation, developing a wide range of craniofacial malformations on an isogenic ..
  9. Tsalavos S, Segklia K, Passa O, Petryk A, O Connor M, Graf D. Involvement of twisted gastrulation in T cell-independent plasma cell production. J Immunol. 2011;186:6860-70 pubmed publisher
    ..In this article, we report that Twisted gastrulation (TWSG1), an extracellular regulator of BMP signaling, is expressed in activated B cells and regulates T-independent B ..

More Information


  1. Petryk A, Anderson R, Jarcho M, Leaf I, Carlson C, Klingensmith J, et al. The mammalian twisted gastrulation gene functions in foregut and craniofacial development. Dev Biol. 2004;267:374-86 pubmed
    ..The Twisted gastrulation (Twsg1) gene product is a small, secreted cysteine-rich protein that has the unusual property of being able to either ..
  2. Zakin L, De Robertis E. Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development. Development. 2004;131:413-24 pubmed
    Twisted gastrulation (Tsg) is a secreted protein that regulates Bmp signaling in the extracellular space through its direct interaction with Bmp/Dpp and Chordin (Chd)/Short gastrulation (Sog)...
  3. MacKenzie B, Wolff R, Lowe N, Billington C, Peterson A, Schmidt B, et al. Twisted gastrulation limits apoptosis in the distal region of the mandibular arch in mice. Dev Biol. 2009;328:13-23 pubmed publisher
    ..BMP activity is modulated in the extracellular space by BMP-binding proteins such as Twisted gastrulation (TWSG1)...
  4. Graf D, Timmons P, Hitchins M, Episkopou V, Moore G, Ito T, et al. Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation. Mamm Genome. 2001;12:554-60 pubmed
    The twisted gastrulation gene (tsg) encodes a secreted protein required for the correct specification of dorsal midline cell fate during gastrulation in Drosophila...
  5. Melnick M, Petryk A, Abichaker G, Witcher D, Person A, Jaskoll T. Embryonic salivary gland dysmorphogenesis in Twisted gastrulation deficient mice. Arch Oral Biol. 2006;51:433-8 pubmed
    Mouse Twisted gastrulation gene (Twsg1) expression is found throughout embryonic development, including substantial levels in the first branchial arch that gives rise to the submandibular salivary gland (SMG)...
  6. Jasuja R, Allen B, Pappano W, Rapraeger A, Greenspan D. Cell-surface heparan sulfate proteoglycans potentiate chordin antagonism of bone morphogenetic protein signaling and are necessary for cellular uptake of chordin. J Biol Chem. 2004;279:51289-97 pubmed
    ..The latter determine cell fates along the embryonic dorsoventral axis. The secreted protein Twisted Gastrulation (TSG) is thought to help shape BMP signaling gradients by acting as a cofactor that enhances Chordin inhibition of BMP ..
  7. Gazzerro E, Deregowski V, Stadmeyer L, Gale N, Economides A, Canalis E. Twisted gastrulation, a bone morphogenetic protein agonist/antagonist, is not required for post-natal skeletal function. Bone. 2006;39:1252-60 pubmed
    Twisted gastrulation (Tsg) is a secreted glycoprotein that binds bone morphogenetic proteins (BMP)-2 and -4 and can display both BMP agonist and antagonist functions...
  8. Graf D, Nethisinghe S, Palmer D, Fisher A, Merkenschlager M. The developmentally regulated expression of Twisted gastrulation reveals a role for bone morphogenetic proteins in the control of T cell development. J Exp Med. 2002;196:163-71 pubmed
    The evolutionarily conserved, secreted protein Twisted gastrulation (Tsg) modulates morphogenetic effects of decapentaplegic (dpp) and its orthologs, the bone morphogenetic proteins 2 and 4 (BMP2/4), in early Drosophila and vertebrate ..
  9. Forsman C, Ng B, Heinze R, Kuo C, Sergi C, Gopalakrishnan R, et al. BMP-binding protein twisted gastrulation is required in mammary gland epithelium for normal ductal elongation and myoepithelial compartmentalization. Dev Biol. 2013;373:95-106 pubmed publisher
    ..Twisted gastrulation (TWSG1) is a secreted BMP binding protein that modulates BMP ligand availability in the extracellular space...
  10. Zakin L, Metzinger C, Chang E, Coffinier C, De Robertis E. Development of the vertebral morphogenetic field in the mouse: interactions between Crossveinless-2 and Twisted Gastrulation. Dev Biol. 2008;323:6-18 pubmed publisher
    Crossveinless-2 (Cv2), Twisted Gastrulation (Tsg) and Chordin (Chd) are components of an extracellular biochemical pathway that regulates Bone Morphogenetic Protein (BMP) activity during dorso-ventral patterning of Drosophila and Xenopus ..
  11. Yamada S, Nakamura J, Asada M, Takase M, Matsusaka T, Iguchi T, et al. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury. PLoS ONE. 2014;9:e89135 pubmed publisher
    ..Here we show that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are ..
  12. Tanno T, Porayette P, Sripichai O, Noh S, Byrnes C, Bhupatiraju A, et al. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood. 2009;114:181-6 pubmed publisher
    ..In this study, erythroblast expression of a second molecule named twisted gastrulation (TWSG1) was explored as a potential erythroid regulator of hepcidin...
  13. Pham L, Beyer K, Jensen E, Rodriguez J, Davydova J, Yamamoto M, et al. Bone morphogenetic protein 2 signaling in osteoclasts is negatively regulated by the BMP antagonist, twisted gastrulation. J Cell Biochem. 2011;112:793-803 pubmed publisher
    ..Similarly, genetic deletion of the BMP antagonist Twisted gastrulation (TWSG1) in mice, resulted in an enhancement of osteoclast formation, activity and osteopenia...
  14. Zakin L, Reversade B, Kuroda H, Lyons K, De Robertis E. Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling in the development of ventral posterior mesoderm. Development. 2005;132:2489-99 pubmed
    ..of bone morphogenetic protein 7 (Bmp7) in combination with a half dose or complete loss of twisted gastrulation (Tsg) causes sirenomelia in the mouse...
  15. Hager Theodorides A, Outram S, Shah D, Sacedon R, Shrimpton R, Vicente A, et al. Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation. J Immunol. 2002;169:5496-504 pubmed
    ..Our study suggests that the BMP2/4 pathway may function in thymic homeostasis by regulating T cell lineage commitment and differentiation. ..
  16. Schmidl M, Adam N, Surmann Schmitt C, Hattori T, Stock M, Dietz U, et al. Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in vitro and in vivo. J Biol Chem. 2006;281:31790-800 pubmed
    Twisted gastrulation (TSG) is an extracellular modulator of bone morphogenetic protein (BMP) activity and regulates dorsoventral axis formation in early Drosophila and Xenopus development...
  17. Gazzerro E, Deregowski V, Vaira S, Canalis E. Overexpression of twisted gastrulation inhibits bone morphogenetic protein action and prevents osteoblast cell differentiation in vitro. Endocrinology. 2005;146:3875-82 pubmed
    Twisted gastrulation (Tsg) is a secreted glycoprotein that binds bone morphogenetic protein-2 (BMP-2) and BMP-4 and can display both BMP agonist and antagonist functions...
  18. Billington C, Schmidt B, Marcucio R, Hallgrimsson B, Gopalakrishnan R, Petryk A. Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice. Dis Model Mech. 2015;8:139-46 pubmed publisher
    ..mice carrying a mutation in a gene encoding the bone morphogenetic protein (BMP) antagonist twisted gastrulation (Twsg1), which is associated with a low penetrance of HPE, are sensitized to retinoic acid (RA) teratogenesis...
  19. Huntley R, Davydova J, Petryk A, Billington C, Jensen E, Mansky K, et al. The Function of Twisted Gastrulation in Regulating Osteoclast Differentiation is Dependent on BMP Binding. J Cell Biochem. 2015;116:2239-46 pubmed publisher
    ..of the major modulators of BMP signaling in the extracellular space is the secreted protein twisted gastrulation (TWSG1), which can inhibit BMP signaling and OCL differentiation...
  20. Walton K, Whidden M, Kolterud Ã, Shoffner S, Czerwinski M, Kushwaha J, et al. Villification in the mouse: Bmp signals control intestinal villus patterning. Development. 2016;143:427-36 pubmed publisher
    ..Rather, a complex cocktail of Bmps and Bmp signal modulators secreted from mesenchymal clusters determines the pattern of villi in a manner that mimics the spread of a self-organizing Turing field. ..
  21. Ikeya M, Nosaka T, Fukushima K, Kawada M, Furuta Y, Kitamura T, et al. Twisted gastrulation mutation suppresses skeletal defect phenotypes in Crossveinless 2 mutant mice. Mech Dev. 2008;125:832-42 pubmed publisher
    ..that skeletal defects in the Cv2-null mutant were reversed by the additional deletion of Twisted gastrulation (Tsg)...
  22. Minoux M, Kratochwil C, Ducret S, Amin S, Kitazawa T, Kurihara H, et al. Mouse Hoxa2 mutations provide a model for microtia and auricle duplication. Development. 2013;140:4386-97 pubmed publisher
    ..Thus, Hoxa2 loss- and gain-of-function approaches in mice provide a suitable model to investigate the molecular aetiology of microtia and auricle duplication. ..