title: Unexpected activities of Smad7 in Xenopus mesodermal and neural induction.
abstract: 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.
authors: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors: Irene
authors: I
authors: de Almeida
authors: Ana
authors: A
authors: Rolo
authors: Julie
authors: J
authors: Batut
authors: Caroline
authors: C
authors: Hill
authors: Claudio D
authors: CD
authors: Stern
authors: Claudia
authors: C
authors: Linker
mesh_terms: D000818:Animals; D002642:Chick Embryo / Q000378:metabolism; D015509:Developmental Biology; D008648:Mesoderm / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D051905:Smad6 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D051905:Smad6 Protein; D051906:Smad7 Protein; C497809:Smad7 protein, Xenopus; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D014212:Tretinoin