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Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled
Author(s) -
Onuma Yasuko,
Takahashi Shuji,
Haramoto Yoshikazu,
Tanegashima Kousuke,
Yokota Chika,
Whitman Malcolm,
Asashima Makoto
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20574
Subject(s) - biology , nodal signaling , wnt signaling pathway , xenopus , microbiology and biotechnology , nodal , signal transduction , endoderm , lrp6 , genetics , embryogenesis , gastrulation , gene , embryonic stem cell , embryo
Nodal and Nodal‐related proteins activate the Activin‐like signal pathway and play a key role in the formation of mesoderm and endoderm in vertebrate development. Recent studies have shown additional activities of Nodal‐related proteins apart from the canonical Activin‐like signal pathway. Here we report a novel function of Nodal‐related proteins using cleavage mutants of Xenopus nodal‐related genes ( cmXnr2 and cmXnr5 ), which are known to be dominant‐negative inhibitors of nodal family signaling. cmXnr2 and cmXnr5 inhibited both BMP signaling and Wnt signaling without activating the Activin‐like signal in animal cap assays. Pro region construct of Xnr2 and Xnr5 did not inhibit Xwnt8 , and pro/mature region chimera mutant cmActivin ‐ Xnr2 and cmActivin‐ Xnr5 also did not inhibit Xwnt8 activity. These results indicate that the pro domains of Xnr2 and Xnr5 are necessary, but not sufficient, for Wnt inhibition, by Xnr family proteins. In addition, Western blot analysis and immunohistochemistry analysis revealed that the unprocessed Xnr5 protein is stably produced and secreted as effectively as mature Xnr5 protein, and that the unprocessed Xnr5 protein diffused in the extracellular space. These results suggest that unprocessed Xnr2 and Xnr5 proteins may be involved in inhibiting both BMP and Wnt signaling and are able to be secreted to act on somewhat distant target cells, if these are highly produced. Developmental Dynamics 234:900–910, 2005. © 2005 Wiley‐Liss, Inc.