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XB-ART-38358
Cell September 5, 2008; 134 (5): 854-65.

Robust stability of the embryonic axial pattern requires a secreted scaffold for chordin degradation.



Abstract
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.

PubMed ID: 18775317
Article link: Cell

Genes referenced: admp bmp1 bmp2 bmp4 bmp7.1 bmp7.2 chdh chrd.1 egr2 en2 gsc myod1 odc1 olfml3 otx2 rax shh sptssb szl tll1
Morpholinos: admp MO1 bmp1 MO1 olfml3 MO1 olfml3 MO2 tll1 MO1


Article Images: [+] show captions
References:
Harland, 2008, Pubmed, Xenbase


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