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.
Highlights
The organization of the axial skeleton and skeletal muscles is bilaterally symmetric
It was proposed that Dmrt2a/Terra maintains the symmetry of somite formation possibly by protecting the presomitic mesoderm (PSM) from the influence of LR asymmetric cues
This protection is only needed in a specific developmental time window that corresponds to the timing of transfer of LR information to the lateral plate mesoderm (LPM) [23]
Summary
The organization of the axial skeleton and skeletal muscles is bilaterally symmetric. In addition to the presence of a molecular clock, the PSM cells are under the influence of a wavefront of differentitaion This wavefront is determined by gradients of Fgf and Wnt signalling coming from the posterior region of the embryo and fading towards the anterior portion of the PSM. Dmrt 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. Dmrt2a/terra is necessary for symmetric somite formation while dmrt2b regulates somite differentiation impacting on slow muscle development. One dmrt gene is expressed in the mouse embryo, where it is necessary for somite differentiation but with an impact on axial skeleton development. Nothing was known about its role during left-right patterning in the lateral plate mesoderm or in the symmetric synchronization of somite formation
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