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Gene Review

cer1  -  cerberus 1, DAN family BMP antagonist

Xenopus laevis

Synonyms: cer, cer-1, dand4, tCerberus, xcer-1, ...
 
 
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Disease relevance of cer

  • Differential screening-selected gene aberrative in neuroblastoma (DAN) belongs to a novel gene family that includes the Xenopus head-inducing factor, Cerberus and the dorsalizing factor, Gremlin [1].
 

High impact information on cer

  • The gene cerberus encodes a secreted protein that is expressed in anterior endoderm and has the unique property of inducing ectopic heads in the absence of trunk structures [2].
  • Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer [3].
  • Therefore, we propose that Gremlin, Cerberus, and DAN control diverse processes in growth and development by selectively antagonizing the activities of different subsets of the TGF beta ligands [4].
  • Addition of exogenous beta-catenin protein induced expression of Siamois, XTwin, Xnr3, and Cerberus mRNAs in a protein synthesis independent manner, whereas a panel of other Spemann organizer-specific genes did not respond to beta-catenin [5].
  • This Hex-mediated enhancement of Wnt signalling results in the upregulation of the Nieuwkoop centre genes Siamois and Xnr3, and the subsequent increased expression of the anterior endodermal marker Cerberus and other mesendodermal genes downstream of Wnt signalling [6].
 

Biological context of cer

 

Anatomical context of cer

  • In Xenopus, XHex and cerberus are early marker genes of the anterior endomesoderm (AE), a subset of endoderm cells fated to form the liver and foregut and implicated in head induction [9].
  • An abundant cDNA enriched in Spemann's organizer, cerberus, was isolated by differential screening [3].
  • Chordin, a marker of the head and axial mesoderm, is activated by the VCC/Siamois pathway in animal cells but not in vegetal cells whereas cerberus, a marker of the anterior mesendoderm which lacks dorsalising activity, can only be activated by the VCC/Siamois pathway in vegetal cells [10].
  • Conjugates of dorsal ectoderm (DE) and ADE explants in which Cerberus function was 'knocked down' revealed the requirement of Cerberus in the ADE for the proper induction of anterior neural markers and repression of more posterior ones [7].
 

Other interactions of cer

  • In overexpression experiments maternal Wnt/beta-catenin and TGF-beta signals (Vg1, Xnr1-2) can induce ectopic XHex and cerberus [9].
  • Surprisingly, dorsal signaling molecules such as Chordin, Noggin, Xnr6 and Cerberus were not re-expressed in these embryos [11].
  • XBF-2 lies downstream of the BMP antagonists noggin, cerberus, and gremlin since ectodermal explants expressing these molecules exhibit strong expression of XBF-2 [12].
 

Analytical, diagnostic and therapeutic context of cer

References

  1. Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn. Ohtori, S., Yamamoto, T., Ino, H., Hanaoka, E., Shinbo, J., Ozaki, T., Takada, N., Nakamura, Y., Chiba, T., Nakagawara, A., Sakiyama, S., Sakashita, Y., Takahashi, K., Tanaka, K., Yamagata, M., Yamazaki, M., Shimizu, S., Moriya, H. Neuroscience (2002) [Pubmed]
  2. The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Piccolo, S., Agius, E., Leyns, L., Bhattacharyya, S., Grunz, H., Bouwmeester, T., De Robertis, E.M. Nature (1999) [Pubmed]
  3. Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer. Bouwmeester, T., Kim, S., Sasai, Y., Lu, B., De Robertis, E.M. Nature (1996) [Pubmed]
  4. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Hsu, D.R., Economides, A.N., Wang, X., Eimon, P.M., Harland, R.M. Mol. Cell (1998) [Pubmed]
  5. A cell-free assay system for beta-catenin signaling that recapitulates direct inductive events in the early xenopus laevis embryo. Nelson, R.W., Gumbiner, B.M. J. Cell Biol. (1999) [Pubmed]
  6. Hex acts with {beta}-catenin to regulate anteroposterior patterning via a Groucho-related co-repressor and Nodal. Zamparini, A.L., Watts, T., Gardner, C.E., Tomlinson, S.R., Johnston, G.I., Brickman, J.M. Development (2006) [Pubmed]
  7. Endogenous Cerberus activity is required for anterior head specification in Xenopus. Silva, A.C., Filipe, M., Kuerner, K.M., Steinbeisser, H., Belo, J.A. Development (2003) [Pubmed]
  8. Expression of the Dan gene during chicken embryonic development. Ogita, J., Isogai, E., Sudo, H., Sakiyama, S., Nakagawara, A., Koseki, H. Mech. Dev. (2001) [Pubmed]
  9. Anterior endomesoderm specification in Xenopus by Wnt/beta-catenin and TGF-beta signalling pathways. Zorn, A.M., Butler, K., Gurdon, J.B. Dev. Biol. (1999) [Pubmed]
  10. Animal and vegetal pole cells of early Xenopus embryos respond differently to maternal dorsal determinants: implications for the patterning of the organiser. Darras, S., Marikawa, Y., Elinson, R.P., Lemaire, P. Development (1997) [Pubmed]
  11. Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos. Reversade, B., Kuroda, H., Lee, H., Mays, A., De Robertis, E.M. Development (2005) [Pubmed]
  12. XBF-2 is a transcriptional repressor that converts ectoderm into neural tissue. Mariani, F.V., Harland, R.M. Development (1998) [Pubmed]
  13. Involvement of BMP-4/msx-1 and FGF pathways in neural induction in the Xenopus embryo. Ishimura, A., Maeda, R., Takeda, M., Kikkawa, M., Daar, I.O., Maéno, M. Dev. Growth Differ. (2000) [Pubmed]
 
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