The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation
- Wei, S., Dai, M., Liu, Z., Ma, Y., Shang, H., Cao, Y., Wang, Q.
- Cell Research 27(2): 202-225 (Journal)
- Registered Authors
- Wang, Qiang
- MeSH Terms
- Body Patterning*
- Cell Line
- Cell Nucleus/metabolism
- Embryo, Nonmammalian/metabolism*
- GTP Phosphohydrolases/metabolism
- Guanine Nucleotide Exchange Factors/metabolism*
- Protein Multimerization
- Wnt Signaling Pathway
- Zebrafish Proteins/metabolism*
- beta Catenin/metabolism*
- p21-Activated Kinases/metabolism
- 27910850 Full text @ Cell Res.
Wei, S., Dai, M., Liu, Z., Ma, Y., Shang, H., Cao, Y., Wang, Q. (2017) The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation. Cell Research. 27(2):202-225.
Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates. Loss- and gain-of-function experiments show that the GEF activity of Net1 is required for the activation of Wnt/β-catenin signaling in zebrafish embryos and mammalian cells. Net1 dissociates and activates PAK1 dimers, and PAK1 kinase activation causes phosphorylation of S675 of β-catenin after MBT, which ultimately leads to the transcription of downstream target genes. In summary, our results reveal that Net1-regulated β-catenin activation plays a crucial role in the dorsal axis formation during zebrafish development.Cell Research advance online publication 2 December 2016; doi:10.1038/cr.2016.141.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes