[The Head Inducer Cerberus in a Multivalent Extracellular Inhibitor]

Overview

Journal J Soc Biol

Specialty Biology

Date 2000 Feb 26

PMID 10689616

Citations 2

Authors

P E Agius

S Piccolo

E M De Robertis

Affiliations

Soon will be listed here.

Abstract

Cerberus encodes for a secreted protein which when overexpressed ventrally in a Xenopus embryo induces head differentiation without trunk (Bouwmeester et al., 1996). We have recently shown that Cerberus can bind BMP-4 (Bone Morphogenetic Protein-4), Xnr-1 (Xenopus Nodal-related 1) and Xwnt-8 in the extracellular space (Piccolo et al., 1999). We present here studies showing that Cerberus does not have a receptor nor a dedicated transduction pathway but rather acts as an extracellular inhibitor. Our results suggest that the action of Cerberus in head induction can be explained by an inhibitory activity upstream of the Nodal-related and BMP-4 receptors. In addition, using dominant negative receptor mutants which block both the Xnr-1 and BMP-4 transduction pathways, we show that this double inhibition is sufficient for head induction in ventral mesoderm explants.

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References

Chen Y, Hata A, Lo R, Wotton D, Shi Y, Pavletich N . Determinants of specificity in TGF-beta signal transduction. Genes Dev. 1998; 12(14):2144-52. PMC: 317013. DOI: 10.1101/gad.12.14.2144. View

Beddington R, Robertson E . Anterior patterning in mouse. Trends Genet. 1998; 14(7):277-84. DOI: 10.1016/s0168-9525(98)01499-1. View

Beddington R, Robertson E . Axis development and early asymmetry in mammals. Cell. 1999; 96(2):195-209. DOI: 10.1016/s0092-8674(00)80560-7. View

Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T . The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature. 1999; 397(6721):707-10. PMC: 2323273. DOI: 10.1038/17820. View

Sasai Y, Lu B, Steinbeisser H, Geissert D, Gont L, De Robertis E . Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. Cell. 1994; 79(5):779-90. PMC: 3082463. DOI: 10.1016/0092-8674(94)90068-x. View

Cho K, Blumberg B, Steinbeisser H, De Robertis E . Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid. Cell. 1991; 67(6):1111-20. PMC: 3102583. DOI: 10.1016/0092-8674(91)90288-a. View

Hemmati-Brivanlou A, Melton D . A truncated activin receptor inhibits mesoderm induction and formation of axial structures in Xenopus embryos. Nature. 1992; 359(6396):609-14. DOI: 10.1038/359609a0. View

Dale L, Howes G, Price B, Smith J . Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. Development. 1992; 115(2):573-85. DOI: 10.1242/dev.115.2.573. View

Zhou X, Sasaki H, Lowe L, Hogan B, Kuehn M . Nodal is a novel TGF-beta-like gene expressed in the mouse node during gastrulation. Nature. 1993; 361(6412):543-7. DOI: 10.1038/361543a0. View

10.

Smith W, Knecht A, Wu M, Harland R . Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm. Nature. 1993; 361(6412):547-9. DOI: 10.1038/361547a0. View

11.

McDonald N, Hendrickson W . A structural superfamily of growth factors containing a cystine knot motif. Cell. 1993; 73(3):421-4. DOI: 10.1016/0092-8674(93)90127-c. View

12.

LAMB T, Knecht A, Smith W, Stachel S, Economides A, Stahl N . Neural induction by the secreted polypeptide noggin. Science. 1993; 262(5134):713-8. DOI: 10.1126/science.8235591. View

13.

Meitinger T, Meindl A, Bork P, Rost B, Sander C, Haasemann M . Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure. Nat Genet. 1993; 5(4):376-80. DOI: 10.1038/ng1293-376. View

14.

Hemmati-Brivanlou A, Melton D . Inhibition of activin receptor signaling promotes neuralization in Xenopus. Cell. 1994; 77(2):273-81. DOI: 10.1016/0092-8674(94)90319-0. View

15.

Schulte-Merker S, Smith J, Dale L . Effects of truncated activin and FGF receptors and of follistatin on the inducing activities of BVg1 and activin: does activin play a role in mesoderm induction?. EMBO J. 1994; 13(15):3533-41. PMC: 395257. DOI: 10.1002/j.1460-2075.1994.tb06660.x. View

16.

Wieser R, Wrana J, Massague J . GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex. EMBO J. 1995; 14(10):2199-208. PMC: 398326. DOI: 10.1002/j.1460-2075.1995.tb07214.x. View

17.

Hoodless P, Haerry T, Abdollah S, Stapleton M, OConnor M, Attisano L . MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell. 1996; 85(4):489-500. DOI: 10.1016/s0092-8674(00)81250-7. View

18.

Isaacs N . Cystine knots. Curr Opin Struct Biol. 1995; 5(3):391-5. DOI: 10.1016/0959-440x(95)80102-2. View

19.

Wilson P, Hemmati-Brivanlou A . Induction of epidermis and inhibition of neural fate by Bmp-4. Nature. 1995; 376(6538):331-3. DOI: 10.1038/376331a0. View

20.

Bouwmeester T, Kim S, Sasai Y, Lu B, De Robertis E . Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer. Nature. 1996; 382(6592):595-601. DOI: 10.1038/382595a0. View