PUBLICATION

Deletion of the chd7 Hinders Oligodendrocyte Progenitor Cell Development and Myelination in Zebrafish

Authors

Shi, L., Wang, Z., Li, Y., Song, Z., Yin, W., Hu, B.

ID

ZDB-PUB-230910-59

Date

2023

Source

International Journal of Molecular Sciences 24(17): (Journal)

Registered Authors

Hu, Bing

Keywords

chd7, myelination, oligodendrocyte, zebrafish

MeSH Terms

CHARGE Syndrome*/genetics
Cell Differentiation/genetics
Animals
DNA Helicases/genetics
Oligodendroglia
Oligodendrocyte Precursor Cells*
Zebrafish/genetics

(all 7)

PubMed

37686337 Full text @ Int. J. Mol. Sci.

Abstract

CHD7, an encoding ATP-dependent chromodomain helicase DNA-binding protein 7, has been identified as the causative gene involved in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia choanae, Retardation of growth and/or development, Genital abnormalities and Ear abnormalities). Although studies in rodent models have expanded our understanding of CHD7, its role in oligodendrocyte (OL) differentiation and myelination in zebrafish is still unclear. In this study, we generated a chd7-knockout strain with CRISPR/Cas9 in zebrafish. We observed that knockout (KO) of chd7 intensely impeded the oligodendrocyte progenitor cells' (OPCs) migration and myelin formation due to massive expression of chd7 in oilg2⁺ cells, which might provoke upregulation of the MAPK signal pathway. Thus, our study demonstrates that chd7 is critical to oligodendrocyte migration and myelination during early development in zebrafish and describes a mechanism potentially associated with CHARGE syndrome.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
chd7	AB	standard conditions	Long-pec	brain	ISH	Figure 1
chd7	AB	standard conditions	Protruding-mouth	brain	ISH	Figure 1
chd7	AB	standard conditions	Long-pec	eye	ISH	Figure 1
chd7	AB	standard conditions	Protruding-mouth	eye	ISH	Figure 1
chd7	AB	standard conditions	Long-pec	spinal cord	ISH	Figure 1
chd7	AB	standard conditions	Protruding-mouth	spinal cord	ISH	Figure 1
chd7	AB	standard conditions	Prim-5	whole organism	RTPCR	Figure 1
chd7	AB	standard conditions	Shield	whole organism	RTPCR	Figure 1
chd7	AB	standard conditions	Protruding-mouth	whole organism	RTPCR	Figure 1
chd7	AB	standard conditions	Long-pec	whole organism	RTPCR	Figure 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	eye morphology, abnormal	Figure 3
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	head decreased size, abnormal	Figure 3
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	pericardium edematous, abnormal	Figure 3
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	post-vent region curved, abnormal	Figure 3
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	whole organism flnbb expression decreased amount, abnormal	Figure 7
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	whole organism mbpa expression decreased amount, abnormal	Figure 5
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	whole organism nr4a1 expression decreased amount, abnormal	Figure 7
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	whole organism olig2 expression decreased amount, abnormal	Figure 5
chd7^ah517/ah517 (AB)	standard conditions	Protruding-mouth	whole organism tnfrsf1a expression increased amount, abnormal	Figure 7
chd7^ah517/ah517 (AB)	standard conditions	Day 5	Mauthner neuron myelin sheath decreased thickness, abnormal	Figure 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ah517		Small Deletion	chd7
ue2Tg	Tg(mbp:EGFP-CAAX)	Transgenic Insertion
vu12Tg	Tg(olig2:EGFP)	Transgenic Insertion

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
CHARGE syndrome	chd7^ah517/ah517 (AB)	standard conditions	TAS

Sequence Targeting Reagents

Target	Reagent	Reagent Type
chd7	CRISPR15- chd7	CRISPR

Fish

Fish
AB
chd7^ah517/ah517 (AB)
chd7^ah517/ah517; ue2Tg (AB)
chd7^ah517/ah517; vu12Tg (AB)
ue2Tg (AB)
vu12Tg (AB)

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab31-gapdh	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Shi et al., 2023 ZDB-PUB-230910-59 PMID:37686337

Deletion of the chd7 Hinders Oligodendrocyte Progenitor Cell Development and Myelination in Zebrafish

Shi et al., 2023

ZDB-PUB-230910-59
PMID:37686337