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Dev Biol 2001 Nov 01;2391:118-31. doi: 10.1006/dbio.2001.0420.
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Expression cloning of Xenopus Os4, an evolutionarily conserved gene, which induces mesoderm and dorsal axis.

Zohn IE , Brivanlou AH .

Multiple factors, including members of the FGF, TGF beta, and Wnt family of proteins, are important mediators in the regulation of dorsal-ventral pattern formation during vertebrate development. By using an expression cloning approach to identify novel factors that could regulate dorsal-ventral patterning in the Xenopus embryo, we isolated the Xenopus homologue of the human Os4 gene by virtue of its ability to induce a secondary dorsal axis. While Os4 homologues have been identified in a variety of species, and human Os4 is overexpressed in human tumors, the biological function of Os4 is unknown. To explore the mechanism by which Xenopus Os4 (XOs4) induces a secondary dorsal axis, we used Xenopus explant and whole-embryo assays. The secondary axis induced by XOs4 is distinct from that induced by activation of Wnt or FGF pathways but similar to that induced by inhibition of BMP signaling or activation of an Activin pathway. However, XOs4 did not inhibit BMP signaling in dissociated animal cap explants, indicating that XOs4 does not inhibit BMP signaling. Similar to activation of an Activin-like pathway, expression of XOs4 induces molecular markers for mesoderm in animal cap explants, although expression of gastrula-stage mesodermal markers was very weak and substantially delayed. Yet, XOs4 does not require activity of the Activin signal-transduction pathway for mesoderm induction as dominant-negative components of the Activin/Nodal/Vg1 pathway did not prevent XOs4-mediated induction of mesodermal derivatives. Finally, like Activin/Nodal/Vg1 pathways, XOs4 requires FGF signaling for expression of mesoderm markers. Results presented in this study demonstrate that XOs4 can induce mesoderm and dorsalize ventral mesoderm resulting in ectopic dorsal axis formation, suggesting a role for this large evolutionarily conserved gene family in early development.

PubMed ID: 11784023
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actc1 acvr2b ag1 bmp2 chrd col2a1 ctdsp2 eomes foxh1 gsc hoxb9 inhbb krt12.4 ldb1 lhx1 ncam1 nodal3.2 odc1 sia1 smad10 smad2 smad4 smad7 tbxt twist1 wnt8a
Antibodies: Ncam1 Ab2 Notochord Ab1 Somite Ab3

Disease Ontology terms: cancer
Phenotypes: Xla Wt + ctdsp2 (Fig.1.a, c) [+]

Article Images: [+] show captions