Induction and differentiation during vertebrate embryonic development

Our group works on the mechanism that controls the formation of dorsoventral and anteroposterior axes in vertebrate embryos.

We focus our study on several key developmental processes including induction and patterning of mesoderm and nervous system, and morphogenetic movements. We use Xenopus and zebrafish as models, which are most suitable for in vivo and in vitro functional analyses. Our objective is to understand the common mechanism operating during early development and in certain human diseases. Three research projects are emerged in the group:

- Wnt signaling plays an important role during development and is also implicated in various diseases. One of our long-term projects is the analysis of the mechanism underlying the activation of different Wnt pathways during development, and the identification of small-molecules that could modulate Wnt signaling.

- We recently showed that Dscr6 gene (Down Syndrome Critical Region protein 6), which is located in a region of chromosome 21 responsible for trisomy 21, could trigger mesoderm formation and is required for anterior development, the present project it to further analyse its mode of function in embryonic axis formation.

- The implication of post-transcriptional regulation during muscle development is not fully investigated, we have shown that RBM24 (RNA-Binding Motif 24) is required for myogenesis, but the mechanism is not clear. We are thus continuing our efforts to understand its function in myogenic differentiation.

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Our group work on the mechanism that controls the formation of dorsoventral and anteroposterior axes in vertebrate embryos. We focus our study on several key developmental processes including induction and patterning of mesoderm and nervous system, and morphogenetic movements. We use Xenopus and zebrafish as models, which are most suitable for in vivo and in vitro functional analyses. Our objective is to understand the common mechanism operating during early development and in certain human diseases. Three research projects are emerged in the group:

  • Wnt signaling plays an important role during development and is also implicated in various diseases. One of our long-term projects is the analysis of the mechanism underlying the activation of different Wnt pathways during development, and the identification of small-molecules that could modulate Wnt signaling.
  • We recently showed that Dscr6 gene (Down Syndrome Critical Region protein 6), which is located in a region of chromosome 21 responsible for trisomy 21, could trigger mesoderm formation and is required for anterior development, the present project it to further analyse its mode of function in embryonic axis formation.
  • The implication of post-transcriptional regulation during muscle development is not fully investigated, we have shown that RBM24 (RNA-Binding Motif 24) is required for myogenesis, but the mechanism is not clear. We are thus continuing our efforts to understand its function in myogenic differentiation.

Highlights

  • Transcriptional derepression plays an important role in the regulation of gene expression. We have demonstrated that XDSCR6, a Xenopus homolog of human Down syndrome critical region protein 6, regulates mesoderm and embryonic axis formation through derepression of polycomb group (PcG) proteins. Our studies suggest that it might function to sequester PcG proteins and identify a novel derepression mechanism regulating embryonic induction and axis formation.
  • RNA-binding proteins play an important role to post-transcriptionally regulate gene expression. We found that Seb4 gene is a direct target of MyoD and is required for the expression of myogenic genes. These results reveal that Seb4 acts downstream of MyoD in myogenesis.
  • Wnt signaling plays crucial roles during development and in tissue maintenance in adults. Abnormal activation of Wnt signaling is observed in several types of cancers. Dishevelled (Dvl) is a key molecule in the Wnt pathways. We have worked to develop small-molecule inhibitors of the Dvl PDZ interaction for use in the elucidation of biological processes, and have identified several small molecules that modulate Wnt signaling by blockade of the Dvl PDZ domain.

Future directions

Based on the results obtained during the last few years, we plan to concentrate our efforts in three directions:

  • Wnt signaling plays an important role during development and in various human diseases. Our aim in this research is to analyse of the mechanism underlying the activation of different Wnt pathways during development, and the identification of small-molecules that could interact with the PDZ domain of Dishevelled and modulate Wnt signaling.
  • We showed that Dscr6 gene (Down Syndrome Critical Region protein 6), which is located in a region of chromosome 21 responsible for trisomy 21, could trigger mesoderm formation and is required for anterior development, our future work is to further precise its mode of function in embryonic axis formation through identification and analysis of novel partners that interact with Dscr6 protein.
  • The implication of post-transcriptional regulation during muscle development is not fully investigated, we showed that RBM24 (RNA-Binding Motif 24) is required for myogenesis, but the mechanism is not clear. We will continue our efforts to understand its function in myogenic differentiation by the identification of its partners and RNA targets.

Collaborations

  • Analysis of Wnt signaling and small-molecules interacting with the PDZ domain of Dishevelled - Department of Structural Biology - St. Jude Children’s Research Hospital - Memphis, USA
  • Genome-editing and generation of mutants using Talens or CRISPR/Cas9 system in zebrafish - School of Life Science - Shandong University - Jinan, China