High Mobility Group B Proteins Regulate Mesoderm Formation And Dorsoventral Patterning During Zebrafish And Xenopus Early Development

It is a complex process for a vertebrate embryo developing from a fertilized egg into a well-organized animal. Among the first major events that happen during the development of a vertebrate embryo, there is the induction of the three germ layers and the patterning of the embryonic axes (anteroposterior axis, dorsoventral axis and left-right axis) before and during gastrulation, so that different regions of the embryo acquire their corresponding fate. The high mobility group (HMG) proteins constitute a superfamily of nuclear proteins that regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure, and the formation of multiple protein complexes on promoter/enhancer regions, but their function in germ layer specification during early development is not clear. Here we show that hmgb genes regulate mesoderm formation and dorsoventral patterning both in zebrafish and Xenopus early embryos. Overexpression of hmgb3blocks the expression of the pan-mesoderm gene no tail/Xbra and other ventrolateral mesoderm genes, and results in embryos with shortened anteroposterior axis, while overexpression of hmgb3EnR, which contains the engrailed repressor domain, most potently repressed no toil expression and mesoderm formation. However, hmgb3VP16, which contains the transcriptional activation domain of VP16, had an opposite effect, indicating that hmgb3may function as a repressor during mesoderm induction and patterning. In addition, we show that hmgb3inhibits target gene expression downstream of mesoderm-inducing factors. Furthermore, using reporter gene assays in Xenopus whole embryos, we show that hmgb3differentially regulates the activation of various mesendoderm reporter genes. In particular, it up-regulates the goosecoid, but inhibits the Xbra reporter gene activation. Therefore, our results suggest that hmgb genes may function to fine-tune the specification and/or dorsoventral patterning of mesoderm during zebrafish and Xenopus development.