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Development 2003 Sep 01;13017:4047-56. doi: 10.1242/dev.00633.
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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: [+]

Species referenced: Xenopus
Genes referenced: bmp1 bmp4 chrd.1 cripto.3 nog pmp22 sox2 tbx2 tll2 tubb2b twsg1
Morpholinos: chrd.1 MO1 chrd.1 MO2

Article Images: [+] show captions
References [+] :
Abreu, Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. 2002, Pubmed, Xenbase