Journal
DEVELOPMENT
Volume 130, Issue 17, Pages 4047-4056Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.00633
Keywords
twisted-gastrulation; BMP; chordin; tolloid; crossveinless; TGF beta; cell-cell signaling; Xenopus; zebrafish; CR modules
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Funding
- NICHD NIH HHS [R37 HD021502, R01 HD021502, HD 21502-17, R37 HD021502-17] Funding Source: Medline
- NIGMS NIH HHS [R01 GM056326, R56 GM056326, GM 56326] Funding Source: Medline
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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.
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