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

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
adnpa	WT	standard conditions	Long-pec	eye	ISH	Fig. S8
adnpa	WT	standard conditions	Prim-25	eye	ISH	Fig. S8
adnpa	WT	standard conditions	Day 4	eye	ISH	Fig. S8
adnpa	WT	standard conditions	Protruding-mouth	eye	ISH	Fig. S8
adnpa	WT	standard conditions	Prim-5	eye	ISH	Fig. S8
adnpa	WT	standard conditions	Prim-5	forebrain	ISH	Fig. S8
adnpa	WT	standard conditions	Protruding-mouth	forebrain	ISH	Fig. S8
adnpa	WT	standard conditions	Day 4	forebrain	ISH	Fig. S8
adnpa	WT	standard conditions	Prim-25	forebrain	ISH	Fig. S8
adnpa	WT	standard conditions	Long-pec	forebrain	ISH	Fig. S8

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
adnpa^{ihb804/ihb804}	standard conditions	Prim-5	whole organism morphology, normal	Fig. S8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	5-9 somites	central nervous system development process quality, normal	Fig. 8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Prim-5	central nervous system development decreased process quality, abnormal	Fig. 8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Prim-5	central nervous system Wnt signaling pathway decreased process quality, abnormal	Fig. 9
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Prim-5	whole organism morphology, normal	Fig. S8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Prim-5	whole organism ventralized, abnormal	Fig. S8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Prim-5	Wnt signaling pathway decreased process quality, abnormal	Fig. 9
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Long-pec	brain dlx5a expression decreased amount, abnormal	Fig. 8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Long-pec	brain neurod1 expression decreased amount, abnormal	Fig. 8
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}	standard conditions	Long-pec	brain phox2a expression decreased amount, abnormal	Fig. 8

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ihb804		Small Deletion	adnpa
ihb805		Small Deletion	adnpb
knu3Tg	Tg(elavl3:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
adnpa	CRISPR1-adnpa	CRISPR
adnpb	CRISPR1-adnpb	CRISPR

Fish

Fish
adnpa^{ihb804/ihb804}
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}
adnpa^{ihb804/ihb804}; adnpb^{ihb805/ihb805}; knu3Tg
adnpb^{ihb805/ihb805}
knu3Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Sun et al., 2020 ZDB-PUB-200615-6 PMID:32533114

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

Sun et al., 2020

ZDB-PUB-200615-6
PMID:32533114