Suppression of head formation by Xmsx-1 through the inhibition of intracellular nodal signaling

It is well established that in Xenopus, bone morphogenetic protein (BMP) ve ntralizes the early embryo through the activation of several target genes e ncoding homeobox proteins, some of which are known to be necessary and suff icient for ventralization. Here, we used an inhibitory form of Xmsx-1, one of BMP's targets, to examine its role in head formation. Interestingly, ven tral overexpression of a dominant Xmsx-1 inhibitor induced an ectopic head with eyes and a cement gland in the ventral side of the embryo, suggesting that Xmsx-1 is normally required to suppress head formation in the ventral side. Supporting this observation, we also found that wild-type Xmsx-1 supp resses head formation through the inhibition of nodal signaling, which is k nown to induce head organizer genes such as cerberus, Xhex and Xdkk-1. We p ropose that negative regulation of the BMP/Xmsx-1 signal is involved not on ly in neural induction but also in head induction and formation. We further suggest that the inhibition of nodal signaling by Xmsx-1 may occur intrace llularly, through interaction with Smads, at the level of the transcription al complex, which activates the activin responsive element.