The Smads are a family of proteins with functions that include the transduction of signalling by the transforming growth factor-β superfamily, which includes the bone morphogenetic proteins (BMPs). In Developmental Cell, LeSueur et al. report that Smad10, a newly identified Smad in Xenopus, is essential for the formation of the frog nervous system.

Smad10 seems to belong to the class of molecules known as common Smads (co-Smads), which associate with receptor-regulated Smads (R-Smads). These, in turn, interact directly with TGF-β ligand–receptor complexes. The only other known co-Smad is Smad4, which is structurally very similar to Smad10. To analyse the function of Smad10, the authors used two loss-of-function approaches — they injected Xenopus embryos with a dominant-negative form of Smad10 or with an antisense oligonucleotide. In both cases, the embryos failed to develop a neural tube.

LeSueur et al. then tested the effects of Smad10 inhibition on the activity of two neural inducers — fibroblast growth factor (FGF), which induces posterior neural tissue, and the BMP inhibitor noggin, which induces anterior neural tissue — in uncommitted ectodermal tissue explants. They found that inhibiting Smad10 prevented the activation of posterior neural markers by FGF, and of anterior neural markers by noggin. So, Smad10 is required for the induction of both anterior and posterior neural tissue, by mediating FGF and noggin activity, respectively. The mechanism that is responsible for this dual response has not been fully elucidated, although initial findings indicate that the phosphorylation state of Smad10 is a key factor.

The implications of these findings for other species are not yet known, and no Smad10 homologue has been identified in the mouse or the chick. However, previous studies in mice indicated that Smad4 might not be the only molecule with co-Smad activity, so it is expected that molecules that are functionally — if not structurally — equivalent are waiting to be discovered.