ZFIN ID: ZDB-PUB-161204-10
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.
Date: 2017
Source: Cell Research   27(2): 202-225 (Journal)
Registered Authors: Wang, Qiang
Keywords: none
MeSH Terms:
  • Animals
  • Body Patterning*
  • Cell Line
  • Cell Nucleus/metabolism
  • Embryo, Nonmammalian/metabolism*
  • Female
  • GTP Phosphohydrolases/metabolism
  • Guanine Nucleotide Exchange Factors/metabolism*
  • Humans
  • Phosphorylation
  • Phosphoserine/metabolism
  • Protein Multimerization
  • Wnt Signaling Pathway
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
  • beta Catenin/metabolism*
  • p21-Activated Kinases/metabolism
PubMed: 27910850 Full text @ Cell Res.
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.