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Breakthrough in Understanding of Dorsoventral Patterning and Regulatory Mechanism of Wnt Signaling Pathway in Zebrafish

The canonical Wnt signaling is one of main pathways for intracellular signal transduction. It plays a crucial role in the early embryonic development and formation of vertebrate organs. The abnormal activity of Wnt signaling is closely associated with various kinds of human diseases. The activation of Wnt pathway can promote the accumulation of beta-catenin in cell nucleus and in turn regulate the transcriptional expression of downstream genes. However, the functions of canonical Wnt signaling in the development and formation of vertebrate organs remains largely unknown and the intracellular regulatory mechanism of this pathway still needs further investigation.  

Under the supervision of CUI Zongbin, Professor of Institute of Hydrobiology, Chinese Academy of Sciences (IHB), Dr. MO Saijun conducted investigations on the expression and regulation, developmental functions and molecular mechanism of caveolin-1, revealing that both caveolin-1a and -1β are able to regulate the development of zebrafish dorsoventral axis and proving that they can inhibit the activity of canonical Wnt signaling by limiting the transport of  beta-catenin from the cytoplasm to the cell nucleus. The researchers also determined the amino acid sequences that are necessary for the reciprocal interaction between caveolin-1 and beta-catenin through mutagenesis analysis. Since caveolin-1 plays significant roles in the development and progression of various kinds of severe human diseases, findings in the study has provided a firm foundation for further understanding of embryonic development and molecular mechanisms of adult diseases that are associated with caveolin-1, and for the design of small molecular drugs targeting motifs of caveolin-1. Details of this study have been published online Developmental Biology 2010, doi:10.1016/j.ydbio.2010.04.033.