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

Abstract

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.

Aggf1 acts at the top of the genetic regulatory hierarchy in specification of hemangioblasts in zebrafish

“…44 The expression of these markers was not changed in aggf1 morphants compared with control embryos (supplemental Figure 8G-P).…”

Specification of anteroposterior axis by combinatorial signaling during Xenopus development

“…This represents another type of antagonistic interaction involved in patterning the embryonic axes. High‐mobility group proteins were shown to repress trunk and posterior development . In addition, a member of the Fox family, FoxD3, is expressed in the Spemann organizer, and the protein interacts with transcriptional corepressor Grg4 (Groucho‐related gene‐4) of the TLE/Groucho family to induce dorsal mesoderm .…”

The Xenopus homologue of Down syndrome critical region protein 6 drives dorsoanterior gene expression and embryonic axis formation by antagonising polycomb group proteins

“…The −1500/+3 goosecoid and −907/-5 Xnr1 promoter-luciferase reporter plasmid DNAs (Watabe et al, 1995;Cao et al, 2007;Cao et al, 2008) were injected at 100 pg with synthetic mRNAs in the animal pole region at the 2-cell stage, and the luciferase assay was performed using ten early gastrula ectoderm explants as described (Cao et al, 2012). The experiments were carried out in triplicate using different batches of embryos and the data were analysed using Student's t-test.…”