Furthermore, in most dact3b genes the 3rd exon was lost. Thus, specifically in teleosts, dact3 genes directly may have evolved into a less potent version of dact1. Amongst gnathostome Dacts, however, Dact4 is the most derived. The protein lost, modified and gained a number of motifs. Significantly, the lost motifs encompass the leucine zipper. thus, the proteins are unable to dimerize. The modified motifs encompass the internal and the C terminal Dvl binding domain, and hence, Dact4 proteins may be unable to regulate this key molecule essential for all Wnt pathways. Since some motifs have been maintained and new motifs have been stabilized, we can assume, however, that the protein is able to carry out some protein protein interactions. This may lead to a sequestering of Dact interacting proteins, and hence the antagonization of Dact1,2,3 function.

The combinatorial expression of Dact genes may determine the outcome of Wnt and TgfB signaling events in gnathostomes In addition to gene loss or sub and neo functionalization, duplicated genes may diversify at the level of their cis regulatory sequences, leading to expression divergence. However, our expression analysis of mouse, chicken, Xenopus and zebrafish dacts suggests that at the pharyngula early somite stage of development, Dact genes are co expressed in many tissues. Notably, most Dact1 and 2 genes, and where present, Dact3 dact3a genes were expressed in the paraxial mesoderm, the fin limb buds and the craniofacial mesenchyme and pharyngeal arches, suggesting that they are the sites of original Dact function before the split of the Dact1 3 and Dact2 4 groups.

Carfilzomib This coexpression furthermore suggests that in a given tissue, the outcome of Wnt and TgfB signaling events depends on the combinatorial activity of these Dacts. In the zebrafish, dact3b and dact4 genes are mainly expressed in the brain, nevertheless still labeling the pharyngeal arches and the pectoral fin buds. The latter is remarkable since the expression of a retrotranscribed gene depends on the regulatory elements present at the integration site. It could be speculated that this potential anti dact has been kept since, together with the original dact4, it may counterbal ance the function of the numerous dact1 3 gene products. However, the net outcome of Dact function in mouse and chicken and in the fish may be similar. Conclusions This study traced the evolution of Dact genes and with it, the evolution of a molecular system that allows the simultaneous control of Wnt and TgfB signaling. Our study suggests that Dacts are chordate specific, with gnathostome Dact1 3 having arisen from one, Dact2 4 from the second precursor generated after 2R.