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First published online July 11, 2008

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Nodal pro-domain sends the right signals

Nodal proteins are TGFβ-related, secreted signalling proteins that play essential roles in vertebrate embryonic development. In zebrafish, the Nodal-related factors Cyclops (Cyc) and Squint (Sqt) have overlapping functions during mesoderm induction and behave as short- and long-range morphogens, respectively. But what determines their different signalling activities? On p. 2649, Tian and co-workers report that the pro-domain of Cyc (like other TGFβ-related proteins, Cyc contains a pro-domain and a mature domain) regulates its activity. Unlike other Nodal proteins, Cyc requires its pro-domain for its activity. They identify several pro-domain regions that regulate Cyc signalling activity, including a lysosome-targeting region that, by destabilising the Cyc precursor, restricts the distance over which Cyc acts. Finally, they report that a mutation in a conserved arginine in the Cyc pro-domain increases Cyc activity. This last observation hints at a possible aetiology for human congenital heterotaxia, a defect in left-right asymmetry caused by an identical mutation in human NODAL.

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Related articles in Development:

The pro-domain of the zebrafish Nodal-related protein Cyclops regulates its signaling activities

Jing Tian, Birgit Andrée, C. Michael Jones, and Karuna Sampath
Development 2008 135: 2649-2658. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?