title: The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation.
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.
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hanqiao
authors.initials: H
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D019521:Body Patterning; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D055503:Protein Multimerization; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C000625525:Net1 protein, zebrafish; D029961:Zebrafish Proteins; D051176:beta Catenin; D010768:Phosphoserine; D054462:p21-Activated Kinases; D020558:GTP Phosphohydrolases