crossveinless 2


Gene Symbol: crossveinless 2
Description: BMP-binding endothelial regulator
Alias: 3110056H04Rik, CV-2, Crim3, Cv2, BMP-binding endothelial regulator protein, bone morphogenetic protein-binding endothelial cell precursor-derived regulator, crossveinless-2
Species: mouse
Products:     crossveinless 2

Top Publications

  1. Pi X, Lockyer P, Dyer L, Schisler J, Russell B, Carey S, et al. Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:2214-22 pubmed publisher
    ..We conclude that Bmper is a critical regulator of Bmp-mediated vascular inflammation and that the fine-tuning of Bmp and Bmper levels is essential in the maintenance of normal vascular homeostasis. ..
  2. Helbing T, Rothweiler R, Ketterer E, Goetz L, Heinke J, Grundmann S, et al. BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium. Blood. 2011;118:5040-9 pubmed publisher
    ..In conclusion, the BMP modulator BMPER is a new protective regulator of vascular inflammation that modulates leukocyte adhesion and migration in vitro and in vivo. ..
  3. Moser M, Binder O, Wu Y, Aitsebaomo J, Ren R, Bode C, et al. BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation. Mol Cell Biol. 2003;23:5664-79 pubmed
  4. Zhang J, Huang Y, Qiu L, Nickel J, Sebald W. von Willebrand factor type C domain-containing proteins regulate bone morphogenetic protein signaling through different recognition mechanisms. J Biol Chem. 2007;282:20002-14 pubmed
    ..By analyzing chordin, CHL2 (chordin-like 2), and CV2 (crossveinless 2) as well as their individual VWC domains, we show that the VWC domain is a versatile binding module that in ..
  5. Kamimura M, Matsumoto K, Koshiba Takeuchi K, Ogura T. Vertebrate crossveinless 2 is secreted and acts as an extracellular modulator of the BMP signaling cascade. Dev Dyn. 2004;230:434-45 pubmed
    ..In contrast, a positive regulator has been identified in Drosophila. Named crossveinless 2 (cv-2), this molecule contains five CR domains at the N-terminal half and a von Willebrand factor D domain at ..
  6. Coffinier C, Ketpura N, Tran U, Geissert D, De Robertis E. Mouse Crossveinless-2 is the vertebrate homolog of a Drosophila extracellular regulator of BMP signaling. Gene Expr Patterns. 2002;2:189-94 pubmed
    ..We conclude that CV-2 is an evolutionarily conserved extracellular regulator of the Dpp/BMP signaling pathway. ..
  7. Colasante G, Sessa A, Crispi S, Calogero R, Mansouri A, Collombat P, et al. Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity. Dev Biol. 2009;334:59-71 pubmed publisher
    ..Together, these data provide new insights into the molecular pathways regulated by Arx during telencephalon development. ..
  8. Zakin L, Chang E, Plouhinec J, De Robertis E. Crossveinless-2 is required for the relocalization of Chordin protein within the vertebral field in mouse embryos. Dev Biol. 2010;347:204-15 pubmed publisher
    Bone morphogenetic proteins (BMPs), as well as the BMP-binding molecules Chordin (Chd), Crossveinless-2 (CV2) and Twisted Gastrulation (Tsg), are essential for axial skeletal development in the mouse embryo...
  9. Moreno Miralles I, Ren R, Moser M, Hartnett M, Patterson C. Bone morphogenetic protein endothelial cell precursor-derived regulator regulates retinal angiogenesis in vivo in a mouse model of oxygen-induced retinopathy. Arterioscler Thromb Vasc Biol. 2011;31:2216-22 pubmed publisher
    ..These bring forth the possibility of novel therapeutic approaches for pathological angiogenesis based on manipulation of BMP signaling. ..

More Information


  1. Fenwick M, Mansour Y, Franks S, Hardy K. Identification and regulation of bone morphogenetic protein antagonists associated with preantral follicle development in the ovary. Endocrinology. 2011;152:3515-26 pubmed publisher
  2. Lockyer P, Mao H, Fan Q, Li L, Yu Lee L, Eissa N, et al. LRP1-Dependent BMPER Signaling Regulates Lipopolysaccharide-Induced Vascular Inflammation. Arterioscler Thromb Vasc Biol. 2017;37:1524-1535 pubmed publisher
    ..The new signaling pathway initiated by BMPER/low-density lipoprotein receptor-related protein 1 axis broadens our understanding about BMPER's role in vascular homeostasis. ..
  3. Harada K, Ogai A, Takahashi T, Kitakaze M, Matsubara H, Oh H. Crossveinless-2 controls bone morphogenetic protein signaling during early cardiomyocyte differentiation in P19 cells. J Biol Chem. 2008;283:26705-13 pubmed publisher
    ..We found a bimodal expression of the BMP-binding protein Crossveinless-2 (Cv2) during cardiomyocyte differentiation; Cv2 is temporally expressed earlier than cardiac transcription factors such ..
  4. Esser J, Rahner S, Deckler M, Bode C, Patterson C, Moser M. Fibroblast growth factor signaling pathway in endothelial cells is activated by BMPER to promote angiogenesis. Arterioscler Thromb Vasc Biol. 2015;35:358-67 pubmed publisher
  5. Wilson D, Phamluong K, Lin W, Barck K, Carano R, Diehl L, et al. Chondroitin sulfate synthase 1 (Chsy1) is required for bone development and digit patterning. Dev Biol. 2012;363:413-25 pubmed publisher
    ..Our results place Chsy1 as an essential regulator of joint patterning and provide a mouse model of human brachydactylies caused by mutations in CHSY1. ..
  6. Heinke J, Wehofsits L, Zhou Q, Zoeller C, Baar K, Helbing T, et al. BMPER is an endothelial cell regulator and controls bone morphogenetic protein-4-dependent angiogenesis. Circ Res. 2008;103:804-12 pubmed publisher
    ..Vice versa, BMP-4 is necessary for BMPER activity. Taken together, BMPER is a dose-dependent endothelial cell activator that plays a unique and pivotal role in fine-tuning BMP activity in angiogenesis. ..
  7. 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 ..
  8. 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
    ..In this report, we show that the augmentation of BMP signaling by a BMP-binding secreted factor, Crossveinless2 (Cv2), is essential for the early embryonic development of mammalian nephrons...
  9. McGarvey A, Rybtsov S, Souilhol C, Tamagno S, Rice R, Hills D, et al. A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation. J Exp Med. 2017;214:3731-3751 pubmed publisher
    ..These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture. ..
  10. Dyer L, Wu Y, Moser M, Patterson C. BMPER-induced BMP signaling promotes coronary artery remodeling. Dev Biol. 2014;386:385-94 pubmed publisher
    ..Together, these results indicate that BMPER-regulated BMP signaling is critical for coronary plexus remodeling and normal coronary artery development. ..
  11. Heinke J, Kerber M, Rahner S, Mnich L, Lassmann S, Helbing T, et al. Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior. Oncogene. 2012;31:2919-30 pubmed publisher
    ..Taken together, these data unequivocally demonstrate that the BMP modulator BMPER is highly expressed in malignant tumors and tumor growth is dependent on the presence of BMPER. ..
  12. Coffinier C, Ketpura N, Tran U, Geissert D, De Robertis E. Mouse Crossveinless-2 is the vertebrate homolog of a Drosophila extracellular regulator of BMP signaling. Mech Dev. 2002;119 Suppl 1:S179-84 pubmed
    ..We conclude that CV-2 is an evolutionarily conserved extracellular regulator of the Dpp/BMP signaling pathway. ..
  13. Russo L, Abdeltawab N, O Brien A, Kotb M, Melton Celsa A. Mapping of genetic loci that modulate differential colonization by Escherichia coli O157:H7 TUV86-2 in advanced recombinant inbred BXD mice. BMC Genomics. 2015;16:947 pubmed publisher
    ..The identification of the QTL on chromosome 9 supports our hypothesis that individual genetic makeup affects the level of colonization after infection with STEC O157:H7. ..
  14. Jumabay M, Zhumabai J, Mansurov N, Niklason K, Guihard P, Cubberly M, et al. Combined effects of bone morphogenetic protein 10 and crossveinless-2 on cardiomyocyte differentiation in mouse adipocyte-derived stem cells. J Cell Physiol. 2017;: pubmed publisher
    ..Crossveinless-2 (CV2, also known as BMP endothelial cell precursor derived regulator [BMPER]) is a BMP-binding protein that modulates ..
  15. Inoue K, Hirose M, Inoue H, Hatanaka Y, Honda A, Hasegawa A, et al. The Rodent-Specific MicroRNA Cluster within the Sfmbt2 Gene Is Imprinted and Essential for Placental Development. Cell Rep. 2017;19:949-956 pubmed publisher
    ..Our study has provided experimental evidence for the indispensable roles of placental miRNAs in trophoblast proliferation and thus fetal development. ..
  16. Caruana G, Cullen McEwen L, Nelson A, Kostoulias X, Woods K, Gardiner B, et al. Spatial gene expression in the T-stage mouse metanephros. Gene Expr Patterns. 2006;6:807-25 pubmed
    ..This study has identified genes spatially expressed in regions of the developing kidney involved in branching morphogenesis, nephrogenesis and the development of the collecting duct system, calyces, renal pelvis and ureter. ..
  17. Patel N, Masaratana P, Diaz Castro J, Latunde Dada G, Qureshi A, Lockyer P, et al. BMPER protein is a negative regulator of hepcidin and is up-regulated in hypotransferrinemic mice. J Biol Chem. 2012;287:4099-106 pubmed publisher
    ..Thus Bmper may play an important role in suppressing hepcidin production in hypotransferrinemic mice. ..
  18. 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
    ..We previously demonstrated that the pro-BMP function of Crossveinless 2 (Cv2) is required for axial and non-axial skeletal development in mice...
  19. Yao Y, Jumabay M, Ly A, Radparvar M, Wang A, Abdmaulen R, et al. Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood. 2012;119:5037-47 pubmed publisher
    ..BMP-4 is essential for angiogenesis and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both induced by the activin receptor like-kinase 1 (ALK1) when stimulated by BMP-9...
  20. Willis M, Dyer L, Ren R, Lockyer P, Moreno Miralles I, Schisler J, et al. BMPER regulates cardiomyocyte size and vessel density in vivo. Cardiovasc Pathol. 2013;22:228-40 pubmed publisher
    ..BMPER appears to play a role in regulating both vessel density and cardiac development in vivo; however, BMPER haploinsufficiency does not result in marked effects on cardiac function or adaptation to pressure overload hypertrophy. ..
  21. Helbing T, Herold E, Hornstein A, Wintrich S, Heinke J, Grundmann S, et al. Inhibition of BMP activity protects epithelial barrier function in lung injury. J Pathol. 2013;231:105-16 pubmed publisher
    ..Inhibition of excessive BMP activation could be a new approach to restore epithelial integrity and prevent disruption of epithelial barrier function after lung injury. ..
  22. Cao H, Jheon A, Li X, Sun Z, Wang J, Florez S, et al. The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation. Development. 2013;140:3348-59 pubmed publisher
    ..Our in vivo and in vitro studies reveal a multistep transcriptional program involving the Pitx2:miR-200c/141:noggin regulatory pathway that is important in epithelial cell differentiation and tooth development. ..
  23. Kelley R, Ren R, Pi X, Wu Y, Moreno I, Willis M, et al. A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling. J Cell Biol. 2009;184:597-609 pubmed publisher
    Bmper, which is orthologous to Drosophila melanogaster crossveinless 2, is a secreted factor that regulates Bmp activity in a tissue- and stage-dependent manner...