The pro-BMP activity of Twisted Gastrulation is independent of BMP binding

Michael Oelgeschläger, Bruno Reversade, Juan Larraín, Shawn Little, Mary C. Mullins, E. M. De Robertis

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)4047-4056
Number of pages10
JournalDevelopment
Volume130
Issue number17
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'The pro-BMP activity of Twisted Gastrulation is independent of BMP binding'. Together they form a unique fingerprint.

Cite this