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
-
- Nerve Tissue Proteins/genetics*
- Nerve Tissue Proteins/metabolism
- Wnt Signaling Pathway/genetics*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Mutation
- Gene Expression Regulation, Developmental
- Neurons/cytology
- Neurons/metabolism*
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism
- Mice
- In Situ Hybridization/methods
- Cells, Cultured
- Protein Binding
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- HEK293 Cells
- Cell Differentiation/genetics*
- beta Catenin/genetics*
- beta Catenin/metabolism
- Animals
- Humans
- Mice, Knockout
- Mouse Embryonic Stem Cells/cytology
- Mouse Embryonic Stem Cells/metabolism*
- PubMed
- 32533114 Full text @ Nat. Commun.
Citation
Sun, X., Peng, X., Cao, Y., Zhou, Y., Sun, Y. (2020) ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling. Nature communications. 11:2984.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping