PUBLICATION

The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression

Authors

Gentile, A., Bensimon-Brito, A., Priya, R., Maischein, H.M., Piesker, J., Guenther, S., Gunawan, F., Stainier, D.Y.

ID

ZDB-PUB-210622-50

Date

2021

Source

eLIFE 10: (Journal)

Registered Authors

Bensimon-Brito, Anabela, Maischein, Hans-Martin, Stainier, Didier

Keywords

cardiac development, cell biology, cell extrusion, developmental biology, tissue integrity, zebrafish

Datasets

GEO:GSE162604

MeSH Terms

Heart/physiology*
Snail Family Transcription Factors/genetics*
Snail Family Transcription Factors/metabolism
Gene Expression Regulation*
Zebrafish/genetics
Zebrafish/physiology*
Myocardium/metabolism
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism
Animals
Intermediate Filaments/genetics*

(all 11)

PubMed

34152269 Full text @ Elife

Abstract

The transcription factor Snai1, a well-known regulator of epithelial-to-mesenchymal transition, has been implicated in early cardiac morphogenesis as well as in cardiac valve formation. However, a role for Snai1 in regulating other aspects of cardiac morphogenesis has not been reported. Using genetic, transcriptomic, and chimeric analyses in zebrafish, we find that Snai1b is required in cardiomyocytes for myocardial wall integrity. Loss of snai1b increases the frequency of cardiomyocyte extrusion away from the cardiac lumen. Extruding cardiomyocytes exhibit increased actomyosin contractility basally as revealed by enrichment of p-myosin and α-catenin epitope α-18, as well as disrupted intercellular junctions. Transcriptomic analysis of wild-type and snai1b mutant hearts revealed the dysregulation of intermediate filament genes, including desmin b (desmb) upregulation. Cardiomyocyte-specific desmb overexpression caused increased cardiomyocyte extrusion, recapitulating the snai1b mutant phenotype. Altogether, these results indicate that Snai1 maintains the integrity of the myocardial epithelium, at least in part by repressing desmb expression.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
BFP	bns103Tg; bns193Tg	standard conditions	Long-pec	cardiac muscle cell plasma membrane	IFL	Figure 2 supplement 1
BFP	bns193Tg	standard conditions	Long-pec	myocardium	IFL	Figure 1 supplement 3
BFP	bns193Tg	standard conditions	Long-pec	myocardium	IFL	Figure 1
BFP	bns193Tg	standard conditions	Day 4	myocardium	IFL	Figure 1 supplement 4
BFP	bns193Tg	standard conditions	Long-pec	myocardium	IFL	Figure 1 supplement 1
BFP	snai1b^{bns351/bns351}; bns103Tg; bns193Tg	standard conditions	Long-pec	cardiac muscle cell plasma membrane	IFL	Figure 2 supplement 1
BFP	snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	myocardium	IFL	Figure 1 supplement 3
BFP	snai1b^{bns351/bns351}; bns193Tg	standard conditions	Day 4	myocardium	IFL	Figure 1 supplement 4
BFP	snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	myocardium	IFL	Figure 1
BFP	snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	myocardium	IFL	Figure 1 supplement 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
bns555Tg	standard conditions	Long-pec	heart desmb expression decreased amount, abnormal	Figure 3
bns555Tg	standard conditions	Long-pec	heart snai1b expression increased amount, abnormal	Figure 3
snai1b^{bns351/bns351}	standard conditions	Pec-fin	cardiac muscle cell desmosome morphology, normal	Figure 4 supplement 1
snai1b^{bns351/bns351}; bns103Tg; bns193Tg	standard conditions	Long-pec	myocardium maintenance of apical/basal cell polarity normal process quality, normal	Figure 2 supplement 1
snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	cardiac muscle cell protruding out of myocardium, abnormal	Figure 1
snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	cardiac muscle cell protruding out of myocardium, abnormal	Figure 1 supplement 1
snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	cardiac muscle cell separated from myocardium, abnormal	Figure 1 supplement 1
snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	heart desmb expression increased amount, abnormal	Figure 3
snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	heart looping decreased process quality, abnormal	Figure 1 supplement 1
snai1b^{bns351/bns351}; bns193Tg	standard conditions	Long-pec	myocardium apoptotic process normal occurrence, normal	Figure 1 supplement 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
bns103Tg	Tg(myl7:EGFP-podxl)	Transgenic Insertion
bns193Tg	Tg(myl7:BFP-CAAX)	Transgenic Insertion
bns351		Small Deletion	snai1b
bns555Tg	Tg(−0.2myl7:snai1b-p2a-GFP)	Transgenic Insertion
ncv43Tg	Tg(myl7:mVenus-gmnn)	Transgenic Insertion
s883Tg	Tg(myl7:EGFP-Hsa.HRAS)	Transgenic Insertion
ubs4Tg	Tg(fli1:GAL4FF)	Transgenic Insertion
zf521Tg	Tg(myl7:H2B-GFP)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
snai1b	CRISPR1-snai1b	CRISPR
snai1b	CRISPR2-snai1b	CRISPR
tnnt2a	MO1-tnnt2a	MRPHLNO

Fish

Fish
bns103Tg; bns193Tg
bns193Tg
bns555Tg
s883Tg
snai1b^{bns351/bns351}
snai1b^{bns351/bns351}; bns103Tg; bns193Tg
snai1b^{bns351/bns351}; bns193Tg
snai1b^{bns351/bns351}; bns193Tg
snai1b^{bns351/bns351}; bns193Tg + MO1-tnnt2a
snai1b^{bns351/bns351}; bns555Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
BFP	EFG	BFP
EGFP	EFG	EGFP
GAL4FF	EFG	GAL4FF
GFP	EFG	GFP
Venus	EFG	Venus

Mapping

Gentile et al., 2021 ZDB-PUB-210622-50 PMID:34152269

The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression

Gentile et al., 2021

ZDB-PUB-210622-50
PMID:34152269