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Updated: Jul 6, 2026
Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo
Published on: February 2, 2016
Unexpected activities of Smad7 in Xenopus mesodermal and neural induction
Irene de Almeida1, Ana Rolo, Julie Batut
1Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
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.
Insights
Neural induction is not solely due to BMP pathway inhibition. Smad7
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Signaling
Background:
- Neural induction is a critical developmental process.
- It is widely thought to result from Bone Morphogenetic Protein (BMP) pathway inhibition.
- Conflicting data necessitates re-evaluation of this mechanism.
Purpose of the Study:
- To re-examine the role of BMP inhibition in neural induction.
- To investigate the broader functions of the TGF-beta inhibitor, Smad7.
- To clarify the complex signaling pathways governing early embryonic development.
Main Methods:
- Utilized Xenopus and chick embryos.
- Over-expressed Smad7, a general TGF-beta pathway inhibitor.
- Assessed Smad1 and Smad2 phosphorylation.
- Analyzed expression of mesodermal and neural markers.
- Investigated Smad7's independence from other signaling pathways (Wnt, FGF, Hedgehog, retinoid).
Main Results:
- Smad7 confirmed to inhibit Smad1 and Smad2 phosphorylation.
- Unexpectedly, Smad7 induced dorsal mesodermal markers (Chordin, Brachyury) in Xenopus ventral epidermis.
- Neural markers were induced non-cell-autonomously, dependent on Chordin and Brachyury induction.
- Smad7 exhibited effects beyond TGF-beta pathway inhibition.
- These novel effects were independent of Wnt, FGF, Hedgehog, and retinoid signaling.
- Smad7's functional elements reside outside its MH2 domain.
Conclusions:
- BMP inhibition alone is insufficient for neural induction, even with concurrent Nodal/Activin pathway blockade.
- Smad7 possesses complex activities beyond TGF-beta pathway inhibition.
- Caution is advised when interpreting studies using Smad7 as a specific TGF-beta pathway inhibitor.
