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XB-ART-36587
PLoS One. October 10, 2007; 2 (10): e1004.

Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ layer formation.

Morris SA , Almeida AD , Tanaka H , Ohta K , Ohnuma S .


Abstract
Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination. Here, we show that Xenopus Tsukushi (X-TSK), a member of the secreted small leucine rich repeat proteoglycan (SLRP) family, is expressed in ectoderm, endoderm, and the organizer during early development. We have previously reported that X-TSK binds to and inhibits BMP signaling in cooperation with chordin. We now demonstrate two novel interactions: X-TSK binds to and inhibits signaling by FGF8b, in addition to binding to and enhancement of Xnr2 signaling. This signal integration by X-TSK at the extracellular level has an important role in germ layer formation and patterning. Vegetally localized X-TSK potentiates endoderm formation through coordination of BMP, FGF and Xnr2 signaling. In contrast, X-TSK inhibition of FGF-MAPK signaling blocks ventrolateral mesoderm formation, while BMP inhibition enhances organizer formation. These actions of X-TSK are reliant upon its expression in endoderm and dorsal mesoderm, with relative exclusion from ventrolateral mesoderm, in a pattern shaped by FGF signals. Based on our observations, we propose a novel mechanism by which X-TSK refines the field of positional information by integration of multiple pathways in the extracellular space.

PubMed ID: 17925852
PMC ID: PMC1994590
Article link: PLoS One.
Grant support: Cancer Research UK, Medical Research Council , Cancer Research UK, Medical Research Council

Genes referenced: chrd.1 fgf8 gal.2 gata4 gdf1 gdf3 gsc inhbb mapk1 myc myod1 nodal nodal1 nodal2 odc1 smad1 smad2 t tgfb1 tsku

Morpholinos referenced: tsku MO1

References:
Abe, 2005, Pubmed, Xenbase[+]


Article Images: [+] show captions

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