[The head inducer Cerberus in a multivalent extracellular inhibitor].
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.
Agius
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PE
Howard Hughes Medical Institute, University of California, Los Angeles 90095-1662, USA.
Piccolo
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S
De Robertis
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EM
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004627:Embryonic Induction; D006257:Head / Q000196:embryology*; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008934:Mitogens / Q000378:metabolism; D008954:Models, Biological; D009924:Organ Culture Techniques; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins; D029961:Zebrafish Proteins
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008934:Mitogens; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C525812:bmp4 protein, Xenopus; C525813:bmp4 protein, zebrafish; C100866:cer1 protein, Xenopus; C512832:ndr2 protein, zebrafish; C512833:nodal1 protein, Xenopus; C495248:wnt8a protein, Xenopus