A careful functional analysis should be done to fully understand the extension of the role of these genes. Additional studies on Dmrt genes from ancestor organisms would give insight on the origin and evolution of these genes. The first dmrt gene suggested to have a role unrelated to sexual development was dmrt2. It was detected in zebrafish and mouse PSM and somites and was reported to be absent from gonadal tissues. Indeed, male and female homozygous mouse mutant embryos are obtained with the same frequency. Functional studies in zebrafish showed that Dmrt2a/Terra protects the bilateral symmetric somite formation from the influence of LR cues. Without Dmrt2a/Terra the expression of the cycling genes in the PSM becomes desynchronized and consequently somite formation is no longer synchronized between the left and right sides of the zebrafish axis. In addition, Dmrt2a/Terra was shown to establish asymmetry in the LPM, being necessary to restrict left-specific genes in the left LPM and having an impact in the localization of Succinylsulfathiazole the heart on the left side. In the mouse, these early Dmrt2 roles were not analyzed and only a later function in somite differentiation was reported. To investigate the degree of functional conservation of dmrt2 in mice, we started by characterizing the expression of the PSM Notch-related cycling genes her7 and lfgn. This analysis was restricted to a specific developmental time window, 6–13 somites, which corresponds to the period when LR information is being transferred from the node to the left LPM – the time when PSM must be protected from the influence of these signals. The cyclic expression pattern of her7 and lfgn in dmrt2 null mutants showed no differences between the left and right sides of the PSM and consequently somite formation proceeded in a bilateral symmetric way. In contrast to the zebrafish, where all the cyclic genes identified so far belong to the Notch pathway, in the mouse several PSM cyclic genes are Wnt and Fgf pathway components. Among those are axin2 and sprouty2, which are negative feedback inhibitors of the Wnt and Fgf pathway, Simetryn respectively. Similarly to what happens with the Notch cyclic genes, no desynchronization of axin2 and sprouty2 expression was observed between the left and the right PSM in dmrt2 null mutants. This is in agreement with the idea supported by experimental data and computational modeling that suggest that oscillations in the Notch, Wnt and Fgf pathways are coupled and integrated in one molecular clock. These results reflect a lack of conservation of the role of Dmrt2 during mouse development in what concerns LR synchronization of somite formation. Regarding a possible conservation of Dmrt2 function in establishing the LR asymmetry pathway, we looked at the expression of left-specific genes. In mice embryos mutant for dmrt2 the expression of spaw and pitx2 was restricted to the left LPM and consistently we observed a correct LR disposition of all the internal organs. Once again, these results indicate that mouse Dmrt2 does not play a role in the establishment of the LR asymmetric cascade. During evolution the process of gene duplication is one key driving force for gene functional innovation. The evolutionary significance of gene duplication is explained by the duplication- degeneration-complementation model, which states that the probability of a duplicate gene to be preserved increases with the occurrence of degenerative mutations in its regulatory region.