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Title: The Guanine Nucleotide Exchange Factor Net1 Facilitates the Specification of Dorsal Cell Fates in Zebrafish Embryos by Promoting Maternal β-Catenin Activation
Author: Shi Wei, Miaomiao Dai, Zhaoting Liu, Yuanqing Ma, Hanqiao Shang, Yu Cao, Qiang Wang
Abstract: 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.
Corresponding author: Qiang Wa
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PubYear: 2016
Issue: DOI: 10.1038/cr.2016.141
Journal: Cell Research
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URL: http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2016141a.html