Journal
CELL RESEARCH
Volume 27, Issue 2, Pages 202-225Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2016.141
Keywords
Net1; dorsal axis formation; beta-catenin phosphorylation; PAK1 dimerization; zebrafish
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Funding
- National key research and development program [2016YFA0100503]
- National Natural Science Foundation of China [31322035, 31271532, 31571501, 91519329]
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Wnt/beta-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal beta-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/beta-catenin signaling in zebrafish embryos and mammalian cells. Net1 dissociates and activates PAK1 dimers, and PAK1 kinase activation causes phosphorylation of S675 of beta-catenin after MBT, which ultimately leads to the transcription of downstream target genes. In summary, our results reveal that Net1-regulated beta-catenin activation plays a crucial role in the dorsal axis formation during zebrafish development.
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