The exception selleck is Xen opus, where no dact2 4 representative is present. Here, dact1 has taken over dact2 expression domains such as the emigrating cranial neural crest cells. Notably, in all species, expression domains overlapped, suggesting that Dact genes may regulate TgfB and Wnt signaling in a combinatorial fashion. Discussion Dact multi adapter proteins are important regulators at the intersection of Wnt and TgfB signaling. The aim of this study was to shed light on the evolution of Dact genes and their functional domains and motifs. Here, we identified previously unknown dact genes and show that they arose late in the deuterostome lineage. In gnathostomes, four Dact genes were generated after 2R, and in many extant species, these four genes are still present.

The distribution of functional domains and pro tein motifs suggests that the ancestral Dact function lied with Wnt signaling. a role in TgfB signaling may have emerged later. Motif reduction in particular in the newly identified Dact4 suggests that this protein may counter act the function of the other Dacts. Significantly, many Dact genes are co expressed during development. Hence, the complement of Dact proteins present in a given tissue will determine the outcome of Wnt and TgfB signaling events. Gnathostomes were originally equipped with four Dact paralogs Previous studies identified Dact1,2,3 genes in mouse and humans, a Dact1 and 2 gene in chicken, one dact1 gene in frogs, and a dact1 and 2 gene in zebrafish. Perform ing extensive database searches, we identified numerous gnathostome Dact genes four distinct Dacts were identified in chondrichthyans.

for actinopterygian bony vertebrates, we found five dacts in holosts and four to six in teleosts, and for sarcopterygians, we found four Dacts in Latimeria as well as in anapsid and diapsid reptiles, two in birds, two in amphibians and three in mammals. The phylogenetic analysis of Dact proteins, protein motif comparison and genomic synteny analysis revealed that all these Dacts belong to four paralog groups that arose after 2R rather than by individual gene duplication events. Subsequently, specifically in the tetrapod lineage individual Dact genes were lost, with mammals shedding Dact4, birds loosing Dact3 and Dact4, and amphibians loosing dact2 and dact4.

The presence of Dact4 in the two reptile lineages and the conservation of the Dact4 gene locus in mammals and frogs suggest that in tetrapods, this newly discovered gene persisted well after the split of the amphibian and the various amniote lineages, and was independently shed in frogs, birds and mammals. During the vertebrate 2R, Dact1 3 arose from one and 2 4 from the other Cilengitide precursor The analysis of Dact proteins sequences revealed a number of motifs that distinguish individual Dacts. However, we also found motif or motif variations that suggest a particularly close relationship of Dact1 3 and Dact2 4.