PUBLICATION

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

Authors
Sun, X., Peng, X., Cao, Y., Zhou, Y., Sun, Y.
ID
ZDB-PUB-200615-6
Date
2020
Source
Nature communications   11: 2984 (Journal)
Registered Authors
Peng, Xixia, Sun, Xiaoyun, Sun, Yuhua
Keywords
none
MeSH Terms
  • HEK293 Cells
  • Cells, Cultured
  • Mice
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Protein Binding
  • Cell Differentiation/genetics*
  • Neurons/cytology
  • Neurons/metabolism*
  • beta Catenin/genetics*
  • beta Catenin/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Humans
  • Mice, Knockout
  • Gene Expression Regulation, Developmental
  • Wnt Signaling Pathway/genetics*
  • Animals
  • In Situ Hybridization/methods
  • Mutation
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Mouse Embryonic Stem Cells/cytology
  • Mouse Embryonic Stem Cells/metabolism*
(all 27)
PubMed
32533114 Full text @ Nat. Commun.
Abstract
ADNP (Activity Dependent Neuroprotective Protein) is a neuroprotective protein whose aberrant expression has been frequently linked to neural developmental disorders, including the Helsmoortel-Van der Aa syndrome (also called the ADNP syndrome). However, its role in neural development and pathology remains unclear. Here, we show that ADNP is required for neural induction and differentiation by enhancing Wnt signaling. Mechanistically, ADNP functions to stabilize β-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex: Axin and APC. Loss of ADNP promotes the formation of the degradation complex and β-Catenin degradation via ubiquitin-proteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. In addition, adnp gene disruption in zebrafish leads to defective neurogenesis and reduced Wnt signaling. Our work provides important insights into the role of ADNP in neural development and the pathology of the Helsmoortel-Van der Aa syndrome caused by ADNP gene mutation.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ihb804
    Small Deletion
    ihb805
      Small Deletion
      knu3TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        adnpaCRISPR1-adnpaCRISPR
        adnpbCRISPR1-adnpbCRISPR
        1 - 2 of 2
        Show
        Fish
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping
        No data available