Gene Symbol: Rspo2
Description: R-spondin 2
Alias: 2610028F08Rik, AA673245, D430027K22, ftls, R-spondin-2, R-spondin 2 homolog, cristin-2, cysteine-rich and single thrombospondin domain-containing protein 2, mCristin-2, roof plate-specific spondin-2
Species: mouse
Products:     Rspo2

Top Publications

  1. Yamada W, Nagao K, Horikoshi K, Fujikura A, Ikeda E, Inagaki Y, et al. Craniofacial malformation in R-spondin2 knockout mice. Biochem Biophys Res Commun. 2009;381:453-8 pubmed publisher
    ..To investigate the developmental role of a newly identified activator of Wnt/beta-catenin signaling, Rspo2, we generated and characterized Rspo2(-/-) mice. We found CLP with mild facial skeletal defects in Rspo2(-/-) mice...
  2. Li S, Yen T, Endo Y, Klauzinska M, Baljinnyam B, Macher B, et al. Loss-of-function point mutations and two-furin domain derivatives provide insights about R-spondin2 structure and function. Cell Signal. 2009;21:916-25 pubmed
    ..To analyze Rspo structure and function, we expressed full-length wild-type Rspo2 and Rspo2 point mutants corresponding to Rspo4 variants that have been linked to developmental defects...
  3. Papapietro O, Teatero S, Thanabalasuriar A, Yuki K, Diez E, Zhu L, et al. R-spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea. Nat Commun. 2013;4:1898 pubmed publisher
    ..Our data demonstrate a previously unknown role of R-spondins and Wnt signalling in susceptibility to infectious diarrhoea and identify R-spondin2 as a key molecular link between infection and intestinal homoeostasis. ..
  4. Bell S, Schreiner C, Wert S, Mucenski M, Scott W, Whitsett J. R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis. Development. 2008;135:1049-58 pubmed publisher
    ..We show that the footless insertional mutation creates a severe hypomorphic R-spondin 2 allele (Rspo2(Tg))...
  5. Aoki M, Kiyonari H, Nakamura H, Okamoto H. R-spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb development. Dev Growth Differ. 2008;50:85-95 pubmed
    Mouse R-spondin2 (Rspo2) is a member of the R-spondin protein family, which is characterized by furin-like cysteine-rich domains and a thrombospondin type 1 repeat...
  6. Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W. R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell. 2004;7:525-34 pubmed
    ..a small pool expression screen for modulators of the Wnt/beta-catenin pathway and identified Xenopus R-spondin2 (Rspo2) as a secreted activator of this cascade...
  7. Nam J, Park E, Turcotte T, Palencia S, Zhan X, Lee J, et al. Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb. Dev Biol. 2007;311:124-35 pubmed
    ..Here, we report that targeted inactivation of the mouse Rspo2 gene causes developmental limb defects, especially in the hindlimb...
  8. Nam J, Turcotte T, Yoon J. Dynamic expression of R-spondin family genes in mouse development. Gene Expr Patterns. 2007;7:306-12 pubmed
    ..Our study shows that R-spondin gene transcripts are widely expressed with distinct patterns in mouse at different developmental stages. ..
  9. Nam J, Turcotte T, Smith P, Choi S, Yoon J. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem. 2006;281:13247-57 pubmed
    ..Our findings expand the repertoire of ligands that induce beta-catenin/TCF-dependent gene activation and implicate the presence of active beta-catenin-dependent gene activation in a Wnt-free biological context. ..

More Information


  1. Friedman M, Oyserman S, Hankenson K. Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2. J Biol Chem. 2009;284:14117-25 pubmed publisher
    ..Wnt11 also increases expression of Rspo2 (R-spondin 2), a secreted factor known to enhance Wnt signaling...
  2. Lowther W, Wiley K, Smith G, Callahan R. A new common integration site, Int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences. J Virol. 2005;79:10093-6 pubmed
    ..sites all cluster within a 1-kb region that is 2 to 3 kb 5' of the transcription initiation site of a gene, 2610028F08RIK, whose gene product contains furin-like and thrombospondin-like sequences...
  3. Jin Y, Turcotte T, Crocker A, Han X, Yoon J. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction. Dev Biol. 2011;352:1-13 pubmed publisher
    ..Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice...
  4. Klauzinska M, Baljinnyam B, Raafat A, Rodriguez Canales J, Strizzi L, Greer Y, et al. Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells. J Cell Physiol. 2012;227:1960-71 pubmed publisher
    b>Rspo2 was identified as a novel common integration site (CIS) for the mouse mammary tumor virus (MMTV) in viral induced mouse mammary tumors. Here we show that Rspo2 modulates Wnt signaling in mouse mammary epithelial cells...
  5. Baljinnyam B, Klauzinska M, Saffo S, Callahan R, Rubin J. Recombinant R-spondin2 and Wnt3a up- and down-regulate novel target genes in C57MG mouse mammary epithelial cells. PLoS ONE. 2012;7:e29455 pubmed publisher
    ..expression, we performed a microarray analysis using C57MG mouse mammary epithelial cells treated with recombinant Rspo2 and/or Wnt3a...
  6. Zhu C, Zheng X, Yang Y, Li B, Wang Y, Jiang S, et al. LGR4 acts as a key receptor for R-spondin 2 to promote osteogenesis through Wnt signaling pathway. Cell Signal. 2016;28:989-1000 pubmed publisher
    ..The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood...
  7. Cheng Y, Kawamura K, Takae S, Deguchi M, Yang Q, Kuo C, et al. Oocyte-derived R-spondin2 promotes ovarian follicle development. FASEB J. 2013;27:2175-84 pubmed publisher
  8. Mulvaney J, Yatteau A, Sun W, Jacques B, Takubo K, Suda T, et al. Secreted factor R-Spondin 2 is involved in refinement of patterning of the mammalian cochlea. Dev Dyn. 2013;242:179-88 pubmed publisher
    ..Expression analysis of all four members of the R-Spondin family showed that only R-Spondin2 (Rspo2) is expressed in the cochlea during development of the sensory epithelium...
  9. Boucherat O, Landry Truchon K, Aoidi R, Houde N, Nadeau V, Charron J, et al. Lung development requires an active ERK/MAPK pathway in the lung mesenchyme. Dev Dyn. 2017;246:72-82 pubmed publisher
    ..Lung development necessitates a functional ERK/MAPK pathway in the lung mesenchymal layer in order to coordinate efficient epithelial-mesenchymal interactions. Developmental Dynamics 246:72-82, 2017. © 2016 Wiley Periodicals, Inc. ..
  10. Han X, Jin Y, Tan L, Kosciuk T, Lee J, Yoon J. Regulation of the follistatin gene by RSPO-LGR4 signaling via activation of the WNT/?-catenin pathway in skeletal myogenesis. Mol Cell Biol. 2014;34:752-64 pubmed publisher
    ..We previously showed that RSPO2 promoted myogenic differentiation via activation of WNT/?-catenin signaling in mouse myoblast C2C12 cells in vitro...
  11. Zebisch M, Xu Y, Krastev C, MacDonald B, Chen M, Gilbert R, et al. Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin. Nat Commun. 2013;4:2787 pubmed publisher
    ..structures of the ZNRF3 ectodomain (ZNRF3(ecto)), a signalling-competent Furin1-Furin2 (Fu1-Fu2) fragment of Rspo2 (Rspo2(Fu1-Fu2)), and Rspo2(Fu1-Fu2) in complex with ZNRF3(ecto), or RNF43(ecto)...
  12. Papapietro O, Gruenheid S. [Rspo2 controls C. rodentium infection outcome in mice]. Med Sci (Paris). 2013;29:688-90 pubmed publisher
  13. Bell S, Schreiner C, Hess K, Anderson K, Scott W. Asymmetric limb malformations in a new transgene insertional mutant, footless. Mech Dev. 2003;120:597-605 pubmed
    ..However, dysmorphology of the apical ectodermal ridge was observed in the mutant limb buds. ..
  14. Kawata M, Taniguchi Y, Mori D, Yano F, Ohba S, Chung U, et al. Different regulation of limb development by p63 transcript variants. PLoS ONE. 2017;12:e0174122 pubmed publisher
    ..Our findings contribute to further understanding of the molecular network of limb development. ..
  15. Zebisch M, Jones E. Crystal structure of R-spondin 2 in complex with the ectodomains of its receptors LGR5 and ZNRF3. J Struct Biol. 2015;191:149-55 pubmed publisher
    ..of an ectodomain variant of human LGR5 (hLGR5ecto) complexed with a signalling competent fragment of mouse Rspo2 (mRspo2Fu1-Fu2)...
  16. Kawasaki M, Porntaveetus T, Kawasaki K, Oommen S, Otsuka Tanaka Y, Hishinuma M, et al. R-spondins/Lgrs expression in tooth development. Dev Dyn. 2014;243:844-51 pubmed publisher
    ..R-spondin/Lgr signaling is thus involved in tooth development. ..
  17. Yin X, Yi H, Wu W, Shu J, Wu X, Yu L. R-spondin2 activates hepatic stellate cells and promotes liver fibrosis. Dig Dis Sci. 2014;59:2452-61 pubmed publisher
    ..These findings suggest that R-Spondin2 may promote HSC activation by enhancing the canonical Wnt pathway. ..
  18. Neufeld S, Rosin J, Ambasta A, Hui K, Shaneman V, Crowder R, et al. A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development. Genesis. 2012;50:741-9 pubmed publisher
    ..However, severe hindlimb truncations resulted when Rspo3 and Rspo2 mutations were combined, demonstrating redundant function of these genes.
  19. Rutter M, Wang J, Huang Z, Kuliszewski M, Post M. Gli2 influences proliferation in the developing lung through regulation of cyclin expression. Am J Respir Cell Mol Biol. 2010;42:615-25 pubmed publisher
    ..However, no change in the levels of cyclins D1, D2, or E1 due to altered Gli3 was observed. These findings suggest that Gli2 and not Gli3 is the primary mediator of Shh signaling influencing fetal lung growth through cyclin regulation. ..
  20. Hoekstra E, von Oerthel L, van der Heide L, Kouwenhoven W, Veenvliet J, Wever I, et al. Lmx1a encodes a rostral set of mesodiencephalic dopaminergic neurons marked by the Wnt/B-catenin signaling activator R-spondin 2. PLoS ONE. 2013;8:e74049 pubmed publisher Lmx1a, and additional downstream targets were identified, like Pou4f1, Pbx1, Pitx2, C130021l20Rik, Calb2 and Rspo2. In line with a specific, rostral-lateral (prosomer 2/3) loss of expression of most of these genes during ..
  21. Pazin D, Gamer L, Cox K, Rosen V. Molecular profiling of synovial joints: use of microarray analysis to identify factors that direct the development of the knee and elbow. Dev Dyn. 2012;241:1816-26 pubmed publisher
    ..The knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor-beta/bone morphogenetic protein (TGF?/BMP) and Wnt ..
  22. Hsu P, Wu F, Kudo M, Hsiao C, Hsueh A, Luo C. A naturally occurring Lgr4 splice variant encodes a soluble antagonist useful for demonstrating the gonadal roles of Lgr4 in mammals. PLoS ONE. 2014;9:e106804 pubmed publisher of transfected 293T cells was found to dose-dependently inhibit the LGR4-mediated Wnt signaling induced by RSPO2 or norrin, suggesting that it is capable of ligand absorption and could have a potential role as an antagonist...
  23. Camp J, Badsha F, Florio M, Kanton S, Gerber T, Wilsch Bräuninger M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A. 2015;112:15672-7 pubmed publisher
    ..Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. ..
  24. Takegami Y, Ohkawara B, Ito M, Masuda A, Nakashima H, Ishiguro N, et al. R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification. Biochem Biophys Res Commun. 2016;473:255-264 pubmed publisher
    ..R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation ..
  25. Vidal V, Sacco S, Rocha A, da Silva F, Panzolini C, Dumontet T, et al. The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3. Genes Dev. 2016;30:1389-94 pubmed publisher
    ..Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life. ..