Left-Right Function of dmrt2 Genes Is Not Conserved between Zebrafish and Mouse

Abstract

BackgroundMembers of the Dmrt family, generally associated with sex determination, were shown to be involved in several other functions during embryonic development. Dmrt2 has been studied in the context of zebrafish development where, due to a duplication event, two paralog genes dmrt2a and dmrt2b are present. Both zebrafish dmrt2a/terra and dmrt2b are important to regulate left-right patterning in the lateral plate mesoderm. In addition, dmrt2a/terra is necessary for symmetric somite formation while dmrt2b regulates somite differentiation impacting on slow muscle development. One dmrt2 gene is also expressed in the mouse embryo, where it is necessary for somite differentiation but with an impact on axial skeleton development. However, nothing was known about its role during left-right patterning in the lateral plate mesoderm or in the symmetric synchronization of somite formation.Methodology/Principal FindingsUsing a dmrt2 mutant mouse line, we show that this gene is not involved in symmetric somite formation and does not regulate the laterality pathway that controls left-right asymmetric organ positioning. We reveal that dmrt2a/terra is present in the zebrafish laterality organ, the Kupffer's vesicle, while its homologue is excluded from the mouse equivalent structure, the node. On the basis of evolutionary sub-functionalization and neo-functionalization theories we discuss this absence of functional conservation.Conclusions/SignificanceOur results show that the role of dmrt2 gene is not conserved during zebrafish and mouse embryonic development.

Transcriptional variants of Dmrt1 and expression of four Dmrt genes in the blunt snout bream, Megalobrama amblycephala

“…The zebrafish Dmrt2a and Dmrt2b have been verified to play overlapping roles, but cannot compensate the function for each other when they were knocked down (Liu et al, 2009). Lourenço et al (2010) present that the role of Dmrt2 is not conserved during the zebrafish and mouse embryonic development. High expression of Dmrt3 in the brain in the chicken, mouse (Smith et al, 2002) and M. amblycephala were consist with the key role of Dmrt3 in the development of the brain.…”

Sex dimorphic expression of five dmrt genes identified in the Atlantic cod genome. The fish-specific dmrt2b diverged from dmrt2a before the fish whole-genome duplication

“…Mouse Dmrt5 was recently identified as an important factor in ventral mesencephalic neural fate specification (Gennet et al, 2011), while mouse dmrt6 is expressed at low levels in the embryonic brain without any known function (Kim et al, 2003). Dmrt2 is necessary for somite differentiation with severe implications for axial skeletal development in mice (Sato et al, 2010;Seo et al, 2006), while zebrafish Dmrt2a and Dmrt2b play overlapping roles in the establishment of left-right asymmetry of the body plan (Liu et al, 2009;Lourenço et al, 2010;Saúde et al, 2005). Further, dmrt2a is required for symmetric somite formation in zebrafish, while dmrt2b regulates somite differentiation impacting on slow muscle development.…”

DM Domain Genes: Sexual and Somatic Development During Vertebrate Embryogenesis

“…However, unlike its paralog, it regulates other aspects of somite differentiation affecting slow muscle development (Liu et al, 2009). Surprisingly, neither the regulation of left-right patterning in the mesoderm nor the involvement in symmetric somite formation has been observed for murine Dmrt2 (Lourenço et al, 2010). Instead, mouse embryos lacking the Dmrt2 function showed early somite patterning defects, perturbed somite maturation, abnormal skeletal muscle in myotome and affected onset of myogenesis (Seo et al, 2006;Sato et al, 2010).…”