PUBLICATION

smarce1 mutants have a defective endocardium and an increased expression of cardiac transcription factors in zebrafish

Authors

Castillo-Robles, J., Ramírez, L., Spaink, H.P., Lomelí, H.

ID

ZDB-PUB-181020-23

Date

2018

Source

Scientific Reports 8: 15369 (Journal)

Registered Authors

Lomeli, Hilda, Spaink, Herman P.

Keywords

none

MeSH Terms

Zebrafish Proteins*/genetics
Zebrafish Proteins*/metabolism
Animals
Mutation*
Transcription Factors*/genetics
Transcription Factors*/metabolism
Zebrafish*/embryology
Zebrafish*/genetics
Gene Expression Regulation, Developmental*
Endocardium/embryology*
Chromosomal Proteins, Non-Histone*/genetics
Chromosomal Proteins, Non-Histone*/metabolism
Embryo, Nonmammalian/embryology

(all 13)

PubMed

30337622 Full text @ Sci. Rep.

Abstract

SWI/SNF or BAF chromatin-remodeling complexes are polymorphic assemblies of homologous subunit families that remodel nucleosomes and facilitate tissue-specific gene regulation during development. BAF57/SMARCE1 is a BAF complex subunit encoded in animals by a single gene and is a component of all mammalian BAF complexes. In vivo, the loss of SMARCE1 would lead to the formation of deficient combinations of the complex which might present limited remodeling activities. To address the specific contribution of SMARCE1 to the function of the BAF complex, we generated CRISPR/Cas9 mutations of smarce1 in zebrafish. Smarce1 mutants showed visible defects at 72 hpf, including smaller eyes, abnormal body curvature and heart abnormalities. Gene expression analysis revealed that the mutant embryos displayed defects in endocardial development since early stages, which led to the formation of a misshapen heart tube. The severe morphological and functional cardiac problems observed at 4 dpf were correlated with the substantially increased expression of different cardiac transcription factors. Additionally, we showed that Smarce1 binds to cis-regulatory regions of the gata5 gene and is necessary for the recruitment of the BAF complex to these regions.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	smarce1^una1/una1; twu34Tg	standard conditions	Protruding-mouth	atrial myocardium	IHC	Fig. 2
EGFP	smarce1^una1/una1; twu34Tg	standard conditions	Protruding-mouth	ventricular myocardium	IHC	Fig. 2
EGFP	twu34Tg	standard conditions	Protruding-mouth	atrial myocardium	IHC	Fig. 2
EGFP	twu34Tg	standard conditions	Protruding-mouth	ventricular myocardium	IHC	Fig. 2
gata5	smarce1^una1/una1	standard conditions	Prim-5	atrial endocardium	ISH	Fig. 5
gata5	smarce1^una1/una1	standard conditions	Prim-5	ventricular endocardium	ISH	Fig. 5
gata5	WT	standard conditions	Prim-5	atrial endocardium	ISH	Fig. 5
gata5	WT	standard conditions	Prim-5	ventricular endocardium	ISH	Fig. 5
kdrl	smarce1^una1/una1	standard conditions	20-25 somites	anterior lateral plate mesoderm endothelial cell	ISH	Fig. 5
kdrl	smarce1^una1/una1	standard conditions	5-9 somites	anterior lateral plate mesoderm	ISH	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
smarce1^una1/+; smarce1^una2/+	standard conditions	Day 4	eye decreased size, abnormal	Fig. 1
smarce1^una1/+; smarce1^una2/+	standard conditions	Day 4	heart edematous, abnormal	Fig. 1
smarce1^una1/+; smarce1^una2/+	standard conditions	Day 4	post-vent region curved dorsal, abnormal	Fig. 1
smarce1^una1/una1	standard conditions	20-25 somites	endocardium endothelial cell mislocalised, abnormal	Fig. 5
smarce1^una1/una1	standard conditions	20-25 somites	endocardium formation decreased occurrence, abnormal	Fig. 5
smarce1^una1/una1	standard conditions	Prim-5	endocardium endothelial cell mislocalised, abnormal	Fig. 5
smarce1^una1/una1	standard conditions	Prim-5	endocardium morphogenesis decreased occurrence, abnormal	Fig. 5
smarce1^una1/una1	standard conditions	Prim-15	endocardium endothelial cell mislocalised, abnormal	Fig. 5
smarce1^una1/una1	standard conditions	Prim-15	endocardium morphogenesis decreased occurrence, abnormal	Fig. 5
smarce1^una1/una1	standard conditions	Prim-25	endocardium endothelial cell mislocalised, abnormal	Fig. 5

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
twu34Tg	Tg(myl7:EGFP)	Transgenic Insertion
una1		Small Deletion	smarce1
una2		Small Deletion	smarce1

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
smarce1	CRISPR11-smarce1	CRISPR

Fish

Fish
smarce1^una1/+
smarce1^una1/+; smarce1^una2/+
smarce1^una1/una1
smarce1^una1/una1; twu34Tg
smarce1^una2/una2
twu34Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Castillo-Robles et al., 2018 ZDB-PUB-181020-23 PMID:30337622

smarce1 mutants have a defective endocardium and an increased expression of cardiac transcription factors in zebrafish

Castillo-Robles et al., 2018

ZDB-PUB-181020-23
PMID:30337622