High mobility group B proteins regulate mesoderm formation and dorsoventral patterning during zebrafish and Xenopus early development

• Published in: Mechanisms of development 2012-09, Vol.129 (9-12), p.263-274
• Main Authors: Cao, Jian-Meng, Li, Shang-Qi, Zhang, Hong-Wei, Shi, De-Li
• Format: Article
• Language: English
• Subjects: Animals; Body Patterning - genetics; Body Patterning - physiology; Danio rerio; Development Biology; Dorsoventral patterning; Fetal Proteins; Freshwater; Gene Expression Regulation, Developmental; Goosecoid Protein - genetics; Goosecoid Protein - metabolism; High mobility group; HMGB Proteins - genetics; HMGB Proteins - metabolism; HMGB Proteins - physiology; HMGB3; HMGB3 Protein - genetics; HMGB3 Protein - metabolism; Life Sciences; Mesoderm - growth & development; Mesoderm - metabolism; Mesoderm induction; Repressor Proteins - genetics; Repressor Proteins - metabolism; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Transcriptional Activation - genetics; Up-Regulation; Xenopus; Xenopus - genetics; Xenopus - growth & development; Xenopus - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Zebrafish; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0925-4773; 1872-6356
• DOI: 10.1016/j.mod.2012.07.001

► We examine the function of HMGB proteins in germ layer specification. ► We show that HMGB3 regulates the expression of a subset of mesoderm genes. ► It acts downstream of mesoderm-inducing factors to restrict mesoderm induction. ► It may function to fine-tune the specification and patterning of mesoderm. 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 hmgb3 blocks 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 tail expression and mesoderm formation. However, hmgb3VP16, which contains the transcriptional activation domain of VP16, had an opposite effect, indicating that hmgb3 may function as a repressor during mesoderm induction and patterning. In addition, we show that hmgb3 inhibits target gene expression downstream of mesoderm-inducing factors. Furthermore, using reporter gene assays in Xenopus whole embryos, we show that hmgb3 differentially 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.