The twisted promotion of BMP signalling

During dorsoventral axis patterning, the bone morphogenetic protein (BMP)signalling pathway specifies ventral cell fate. BMP signalling is regulated by complex interactions between the BMP inhibitor Chordin, Tolloid (Tld)-related proteases, which cleave Chordin, and the Chordin-interacting protein Twisted gastrulation (Tsg). Xie and Fisher now report that Tsg enhances BMP signalling in zebrafish gastrula through chordin-dependent and -independent mechanisms(see p. 383). First, by introducing RNAs that encode Chordin proteins lacking Tld cleavage sites into chordin-deficient embryos, the researchers show that the in vivo processing of Chordin by Tld regulates Chordin's activity. Then, they show that the morpholino-based depletion of Tsg increases Chordin levels and decreases BMP signalling. Finally, they demonstrate that Tsg also enhances BMP signalling in the absence of Chordin. Taken together with data reported recently by Little and Mullins (Development 2004: 131, 5825-5835),which reveal that loss of tsg1 in zebrafish causes the dorsalisation of the embryonic axis and suppresses the ventralised phenotypes of Chordin mutants, these results indicate that the main role of Tsg in early zebrafish development is to promote BMP signalling.