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Mech Dev May 1, 2008; 125 (5-6): 421-31.

Unexpected activities of Smad7 in Xenopus mesodermal and neural induction.

de Almeida I , Rolo A , Batut J , Hill C , Stern CD , Linker C .

Neural induction is widely believed to be a direct consequence of inhibition of BMP pathways. Because of conflicting results and interpretations, we have re-examined this issue in Xenopus and chick embryos using the powerful and general TGFbeta inhibitor, Smad7, which inhibits both Smad1- (BMP) and Smad2- (Nodal/Activin) mediated pathways. We confirm that Smad7 efficiently inhibits phosphorylation of Smad1 and Smad2. Surprisingly, however, over-expression of Smad7 in Xenopus ventral epidermis induces expression of the dorsal mesodermal markers Chordin and Brachyury. Neural markers are induced, but in a non-cell-autonomous manner and only when Chordin and Brachyury are also induced. Simultaneous inhibition of Smad1 and Smad2 by different approaches does not account for all Smad7 effects, indicating that Smad7 has activities other than inhibition of the TGFbeta pathway. We provide evidence that these effects are independent of Wnt, FGF, Hedgehog and retinoid signalling. We also show that these effects are due to elements outside of the MH2 domain of Smad7. Together, these results indicate that BMP inhibition is not sufficient for neural induction even when Nodal/Activin is also blocked, and that Smad7 activity is considerably more complex than had previously been assumed. We suggest that experiments relying on Smad7 as an inhibitor of TGFbeta-pathways should be interpreted with considerable caution.

PubMed ID: 18359614
PMC ID: PMC2696275
Article link: Mech Dev
Grant support: [+]
Genes referenced: cer1 chrd.1 gsk3b nodal nodal1 nog shh six3 smad1 smad2 smad6 smad7 sox2 sox3 tbxt tgfb1
Antibodies: Smad1 Ab7 Smad2 Ab3 Smad2 Ab4 Tuba4b Ab14

Article Images: [+] show captions
References [+] :
Bachiller, The organizer factors Chordin and Noggin are required for mouse forebrain development. 2000, Pubmed

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