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
  • Animals
  • Cell Differentiation/genetics*
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Humans
  • In Situ Hybridization/methods
  • Mice
  • Mice, Knockout
  • Mouse Embryonic Stem Cells/cytology
  • Mouse Embryonic Stem Cells/metabolism*
  • Mutation
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Neurons/cytology
  • Neurons/metabolism*
  • Protein Binding
  • Wnt Signaling Pathway/genetics*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • beta Catenin/genetics*
  • beta Catenin/metabolism
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
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes