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Gene Review

chd  -  chordin

Danio rerio

Synonyms: Chordin, Protein chordino, SO:0000704, chordino, chrd, ...
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Disease relevance of chd


High impact information on chd

  • We generated phenocopies of mutations of the genes no tail (ref. 2), chordin (ref. 3), one-eyed-pinhead (ref. 4), nacre (ref. 5) and sparse (ref. 6), removing gene function from maternal through post-segmentation and organogenesis developmental stages [2].
  • Through injections of chd mRNA into the early embryo, we restored wild-type gene expression patterns, and the resultant fish, although genotypically mutant, developed normal axial skeletons and fins [3].
  • Some ventralized mutants recover and develop into fertile adults, thereby revealing a requirement for chd function for the later processes of fin and caudal skeletal patterning [3].
  • Noggin antagonism is thought to prevent osteogenesis at sites of joint formation, whereas chordin has not yet been implicated in skeletogenesis [3].
  • Our results demonstrate that chordin function during gastrulation is important for the correct morphogenesis of the adult zebrafish skeleton [3].

Biological context of chd

  • Lastly we observed a striking increased penetrance of the swirl/bmp2b dominant dorsalized phenotype, when Chordin function is also absent [4].
  • Loss of the BMP antagonist Chordin is expected to increase BMP signaling levels in a swirl heterozygote, but instead we observed an apparent decrease in BMP signaling levels and a loss of ventral tail tissue [4].
  • While injection of BMP4 MO had no effect on WT hematopoiesis, co-injecting BMP4 with chd MOs significantly reduced ICM expansion [5].
  • We show that this early restriction of Bmp gene expression, which occurs independently of noggin and chordin, is an essential step in the establishment of DV patterning [6].
  • Embryonic patterning is highly sensitive to maternal and zygotic ogo gene dosage, especially when the level of zygotic chordin activity is also reduced [7].

Anatomical context of chd

  • Our results suggest that by regulating the expression of her5, the Bmp2b/Chordin gradient directs the anteroposterior patterning of endoderm in zebrafish embryos [8].
  • Furthermore, Chordin was degraded by COS cells expressing Tolloid [9].
  • In the zygote, repression of ventralizing Bmp activity on the dorsal side through chordin and noggin is crucial for establishment of a dorsally located organizer [10].
  • We demonstrate that Tld cleavage is crucial in restricting Chordin function in vivo, and is carried out by redundant enzymes in the zebrafish gastrula [11].
  • We utilized zebrafish mutant combinations that disrupt Chordin and mesoderm formation to reveal additional signals that contribute to the establishment of the neural domain [12].

Enzymatic interactions of chd

  • Thus, the Tolloid/Mini fin metalloprotease that normally cleaves and inhibits Chordin activity is dispensable, when Ogon antagonism is reduced [4].

Regulatory relationships of chd

  • Misexpression of prdm1 inhibits the formation of dorsoanterior structures and reduces expression of chordin, which encodes a BMP antagonist [13].
  • In turn, vox and vent repress chordin expression, restricting its function as an antagonist of ventral fates to the dorsal side of the embryo [14].

Other interactions of chd

  • Overexpression of fgf17b dorsalizes zebrafish gastrulae by enhancing expression of chordin (chd), which is an antagonist of the ventralizing signals BMPs [15].
  • We conclude that bmp1 and mfn gene products functionally overlap and are together responsible for a key portion of the Chordin processing activity necessary to formation of the zebrafish dorsoventral axis [16].
  • Moreover, loss of tsg1 partially suppressed the ventralized phenotypes of mutants of the BMP antagonists Chordin or Sizzled (Ogon) [17].
  • Specifically, Bone Morphogenetic Proteins (Bmps) pattern ventral tissues of the embryo while inhibitors of Bmps, such as Chordin, Noggin and Follistatin, are implicated in dorsal mesodermal and neural development [18].
  • However, this effect was mediated by Chordino (zebrafish Chordin), because Fgf3 induces chordino expression in the epiblast and Fgf3-induced neural expansion was substantially suppressed in dino mutants with mutated chordino genes [19].


  1. Genomic organisation of the human chordin gene and mutation screening of candidate Cornelia de Lange syndrome genes. Smith, M., Herrell, S., Lusher, M., Lako, L., Simpson, C., Wiestner, A., Skoda, R., Ireland, M., Strachan, T. Hum. Genet. (1999) [Pubmed]
  2. Effective targeted gene 'knockdown' in zebrafish. Nasevicius, A., Ekker, S.C. Nat. Genet. (2000) [Pubmed]
  3. Patterning the zebrafish axial skeleton requires early chordin function. Fisher, S., Halpern, M.E. Nat. Genet. (1999) [Pubmed]
  4. Modulation of BMP activity in dorsal-ventral pattern formation by the chordin and ogon antagonists. Wagner, D.S., Mullins, M.C. Dev. Biol. (2002) [Pubmed]
  5. Characterization of expanded intermediate cell mass in zebrafish chordin morphant embryos. Leung, A.Y., Mendenhall, E.M., Kwan, T.T., Liang, R., Eckfeldt, C., Chen, E., Hammerschmidt, M., Grindley, S., Ekker, S.C., Verfaillie, C.M. Dev. Biol. (2005) [Pubmed]
  6. Fgf signalling controls the dorsoventral patterning of the zebrafish embryo. Fürthauer, M., Van Celst, J., Thisse, C., Thisse, B. Development (2004) [Pubmed]
  7. Maternal and zygotic activity of the zebrafish ogon locus antagonizes BMP signaling. Miller-Bertoglio, V., Carmany-Rampey, A., Fürthauer, M., Gonzalez, E.M., Thisse, C., Thisse, B., Halpern, M.E., Solnica-Krezel, L. Dev. Biol. (1999) [Pubmed]
  8. BMP signalling regulates anteroposterior endoderm patterning in zebrafish. Tiso, N., Filippi, A., Pauls, S., Bortolussi, M., Argenton, F. Mech. Dev. (2002) [Pubmed]
  9. Cleavage of the BMP-4 antagonist chordin by zebrafish tolloid. Blader, P., Rastegar, S., Fischer, N., Strähle, U. Science (1997) [Pubmed]
  10. Maternal control of vertebrate dorsoventral axis formation and epiboly by the POU domain protein Spg/Pou2/Oct4. Reim, G., Brand, M. Development (2006) [Pubmed]
  11. Twisted gastrulation enhances BMP signaling through chordin dependent and independent mechanisms. Xie, J., Fisher, S. Development (2005) [Pubmed]
  12. Chordin, FGF signaling, and mesodermal factors cooperate in zebrafish neural induction. Londin, E.R., Niemiec, J., Sirotkin, H.I. Dev. Biol. (2005) [Pubmed]
  13. Essential roles of a zebrafish prdm1/blimp1 homolog in embryo patterning and organogenesis. Wilm, T.P., Solnica-Krezel, L. Development (2005) [Pubmed]
  14. The homeobox genes vox and vent are redundant repressors of dorsal fates in zebrafish. Imai, Y., Gates, M.A., Melby, A.E., Kimelman, D., Schier, A.F., Talbot, W.S. Development (2001) [Pubmed]
  15. fgf17b, a novel member of Fgf family, helps patterning zebrafish embryos. Cao, Y., Zhao, J., Sun, Z., Zhao, Z., Postlethwait, J., Meng, A. Dev. Biol. (2004) [Pubmed]
  16. bmp1 and mini fin are functionally redundant in regulating formation of the zebrafish dorsoventral axis. Jasuja, R., Voss, N., Ge, G., Hoffman, G.G., Lyman-Gingerich, J., Pelegri, F., Greenspan, D.S. Mech. Dev. (2006) [Pubmed]
  17. Twisted gastrulation promotes BMP signaling in zebrafish dorsal-ventral axial patterning. Little, S.C., Mullins, M.C. Development (2004) [Pubmed]
  18. The role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo. Connors, S.A., Trout, J., Ekker, M., Mullins, M.C. Development (1999) [Pubmed]
  19. Inhibition of BMP activity by the FGF signal promotes posterior neural development in zebrafish. Koshida, S., Shinya, M., Nikaido, M., Ueno, N., Schulte-Merker, S., Kuroiwa, A., Takeda, H. Dev. Biol. (2002) [Pubmed]
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