PUBLICATION

Zebrafish smarcc1a mutants reveal requirements for BAF chromatin remodeling complexes in distinguishing the atrioventricular canal from the cardiac chambers

Authors

Auman, H.J., Fernandes, I.H., Berríos-Otero, C.A., Colombo, S., Yelon, D.

ID

ZDB-PUB-230422-49

Date

2023

Source

Developmental Dynamics : an official publication of the American Association of Anatomists 253(1): 157-172 (Journal)

Registered Authors

Yelon, Deborah

Keywords

BAF155, Tbx5, cardiac morphogenesis, cardiac patterning

MeSH Terms

Endocardial Cushions*
Heart
Animals
Chromatin Assembly and Disassembly
Gene Expression Regulation, Developmental
Transcription Factors/genetics
Transcription Factors/metabolism
Zebrafish*/genetics
Zebrafish*/metabolism
Zebrafish Proteins/metabolism
Mammals/metabolism

(all 11)

PubMed

37083132 Full text @ Dev. Dyn.

Abstract

Background Essential patterning processes transform the heart tube into a compartmentalized organ with distinct chambers separated by an atrioventricular canal (AVC). This transition involves the refinement of expression of genes that are first found broadly throughout the heart tube and then become restricted to the AVC. Despite the importance of cardiac patterning, we do not fully understand the mechanisms that limit gene expression to the AVC.

Results We show that the zebrafish gene smarcc1a, encoding a BAF chromatin remodeling complex subunit homologous to mammalian BAF155, is critical for cardiac patterning. In smarcc1a mutants, myocardial differentiation and heart tube assembly appear to proceed normally. Subsequently, the smarcc1a mutant heart fails to exhibit refinement of gene expression patterns to the AVC, and the persistence of broad gene expression is accompanied by failure of chamber expansion. In addition to their cardiac defects, smarcc1a mutants lack pectoral fins, indicating similarity to tbx5a mutants. However, comparison of smarcc1a and tbx5a mutants suggests that perturbation of tbx5a function is not sufficient to cause the smarcc1a mutant phenotype.

Conclusions Our data indicate an important role for Smarcc1a-containing chromatin remodeling complexes in regulating the changes in gene expression and morphology that distinguish the AVC from the cardiac chambers. This article is protected by copyright. All rights reserved.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bmp10	smarcc1a^sk29/sk29	standard conditions	Long-pec	heart	ISH	Fig. 9
bmp10	smarcc1a^sk29/sk29	standard conditions	Long-pec	heart	ISH	Fig. 8
bmp4	smarcc1a^sk29/sk29	standard conditions	Long-pec	heart	ISH	Fig. 7
bmp4	smarcc1a^sk29/sk29	standard conditions	Prim-15	heart tube	ISH	Fig. 7
bmp4	smarcc1a^sk29/sk29	standard conditions	Prim-25	heart tube	ISH	Fig. 7
mCherry	smarcc1a^sk29/sk29; sd12Tg/sd12Tg	standard conditions	Long-pec	atrium cardiac muscle cell	ISH	Fig. 10
mCherry	smarcc1a^sk29/sk29; sd12Tg/sd12Tg	standard conditions	Long-pec	cardiac ventricle cardiac muscle cell	ISH	Fig. 10
mCherry	tbx5a^m21/m21; sd12Tg/sd12Tg	standard conditions	Long-pec	atrium cardiac muscle cell	ISH	Fig. 10
myh6	smarcc1a^sk29/sk29	standard conditions	Long-pec	atrium cardiac muscle cell	ISH	Fig. 5
myh6	smarcc1a^sk29/sk29	standard conditions	Prim-15	presumptive atrium heart tube cardiac muscle cell	ISH	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	atrioventricular canal linear, abnormal	Fig. 3
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	atrioventricular canal tubular, abnormal	Fig. 3
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	melanocyte decreased amount, abnormal	Fig. 3
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	pectoral fin absent, abnormal	Fig. 3
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	pericardium edematous, abnormal	Fig. 3
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	retina decreased size, abnormal	Fig. 3
WT + MO4-smarcc1a + MO5-smarcc1a	standard conditions	Long-pec	retinal pigmented epithelium decreased pigmentation, abnormal	Fig. 3
smarcc1a^sk29/sk29	standard conditions	1-4 somites	whole organism smarcc1a expression decreased amount, abnormal	Fig. 2
smarcc1a^sk29/sk29	standard conditions	10-13 somites	anterior lateral plate mesoderm myl7 expression spatial pattern, abnormal	Fig. 4
smarcc1a^sk29/sk29	standard conditions	14-19 somites	whole organism Ab1-smarcc1 labeling decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b109		Small Deletion	tnnt2a
m21		Point Mutation	tbx5a
sd12Tg	Tg(myl7:h2az2a-mCherry)	Transgenic Insertion
sk29		Point Mutation	smarcc1a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
smarcc1a	MO4-smarcc1a	MRPHLNO
smarcc1a	MO5-smarcc1a	MRPHLNO

Fish

Fish
smarcc1a^sk29/sk29
smarcc1a^sk29/sk29; sd12Tg/sd12Tg
smarcc1a^sk29/sk29; tnnt2a^b109/b109
tbx5a^m21/m21
tbx5a^m21/m21; sd12Tg/sd12Tg
tnnt2a^b109/b109
WT + MO4-smarcc1a + MO5-smarcc1a

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-smarcc1	monoclonal		IgG	Rabbit
Ab6-cdh2	polyclonal		IgG	Rabbit
Ab-S46	monoclonal	myh6	IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
mCherry	EFG	mCherry

Mapping

Auman et al., 2023 ZDB-PUB-230422-49 PMID:37083132

Zebrafish smarcc1a mutants reveal requirements for BAF chromatin remodeling complexes in distinguishing the atrioventricular canal from the cardiac chambers

Auman et al., 2023

ZDB-PUB-230422-49
PMID:37083132