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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 .

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 , R01 GM056326 NIGMS NIH HHS , R01 HD021502 NICHD NIH HHS , R56 GM056326 NIGMS NIH HHS

Genes referenced: bmp1 bmp4 chrd.1 myod1 nog pclo pmp22 sox2 tbx2 tdgf1.3 tll2 tubb2b twsg1

Morpholinos referenced: chrd MO1 chrd MO2

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Abreu, 2002, Pubmed, Xenbase[+]

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