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XB-ART-4966
Development. September 1, 2003; 130 (17): 4047-56.

The pro-BMP activity of Twisted gastrulation is independent of BMP binding.

Oelgeschläger M , Reversade B , Larraín J , Little S , Mullins MC , De Robertis EM .


Abstract
The determination of the vertebrate dorsoventral body axis is regulated in the extracellular space by a system of interacting secreted molecules consisting of BMP, Chordin, Tolloid and Twisted Gastrulation (Tsg). Tsg is a BMP-binding protein that forms ternary complexes with BMP and Chordin. We investigated the function of Tsg in embryonic patterning by generating point mutations in its two conserved cysteine-rich domains. Surprisingly, Tsg proteins with mutations in the N-terminal domain were unable to bind BMP, yet ventralized the embryo very effectively, indicating strong pro-BMP activity. This hyperventralizing Tsg activity required an intact C-terminal domain and could block the anti-BMP activity of isolated BMP-binding modules of Chordin (CRs) in embryonic assays. This activity was specific for CR-containing proteins as it did not affect the dorsalizing effects of Noggin or dominant-negative BMP receptor. The ventralizing effects of the xTsg mutants were stronger than the effect of Chordin loss-of-function in Xenopus or zebrafish. The results suggest that xTsg interacts with additional CR-containing proteins that regulate dorsoventral development in embryos.

PubMed ID: 12874126
PMC ID: PMC2277362
Article link: Development.
Grant support: GM 56326 NIGMS NIH HHS , HD 21502-17 NICHD NIH HHS , R37 HD021502-17 NICHD NIH HHS , R37 HD021502 NICHD NIH HHS

Genes referenced: bmp1 bmp4 chrd myod1 nog pclo pmp22 sox2 tdgf1.3 tll2 tubb2b twsg1
Antibodies referenced:
Morpholinos referenced: chrd MO1 chrd MO2
Article Images: [+] show captions

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