Robust stability of the embryonic axial pattern requires a secreted scaffold for chordin degradation.
Dorsal axial formation during vertebrate embryogenesis exhibits robust resistance to perturbations in patterning signals. However, how such stability is supported at the molecular level remains largely elusive. Here we show that Xenopus ONT1, an Olfactomedin-class secreted protein, stabilizes axial formation by restricting Chordin activity on the dorsal side. When ONT1 function is attenuated, the embryo becomes hyperdorsalized by a normally subeffective dose of Chordin. ONT1 binds Chordin and BMP1/Tolloid-class proteinases (B1TP) via distinct domains and acts as a secreted scaffold that enhances B1TP-mediated Chordin degradation by facilitating enzyme-substrate association. ONT1 is indispensable for fine-tuning BMP signaling in the axial tissue, and a similar role has been suggested for dorsally expressed BMPs such as ADMP. Simultaneous inhibition of ONT1 and dorsally expressed BMPs (ADMP and BMP2) synergistically caused drastic dorsalization. These results indicate that stable axial formation depends on two compensatory regulatory pathways involving ONT1/B1TP and dorsally expressed BMPs.
Inomata
Hidehiko
H
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Haraguchi
Tomoko
T
Sasai
Yoshiki
Y
D000818:Animals; D019521:Body Patterning; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D004625:Embryo, Nonmammalian / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D055394:Tolloid-Like Metalloproteinases; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D029867:Xenopus Proteins; C081451:olfactomedin; C054234:chordin; D045726:Metalloproteases; D055394:Tolloid-Like Metalloproteinases; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1