PUBLICATION

Lamb1a regulates atrial growth by limiting second heart field addition during zebrafish heart development

Authors

Derrick, C.J., Pollitt, E.J.G., Sevilla Uruchurtu, A.S., Hussein, F., Grierson, A.J., Noël, E.S.

ID

ZDB-PUB-210928-13

Date

2021

Source

Development (Cambridge, England) 148(20): (Journal)

Registered Authors

Derrick, Chris, Noël, Emily

Keywords

Contractility, Extracellular matrix, Heart development, Laminin, Second heart field, Zebrafish

MeSH Terms

Organogenesis/physiology
Animals
Morphogenesis/physiology
Laminin/metabolism*
Heart Defects, Congenital/metabolism
Myocardium/metabolism
Zebrafish/metabolism*
Zebrafish Proteins/metabolism*
Heart/physiology*
Cell Lineage/physiology
Heart Atria/metabolism*
Gene Expression Regulation, Developmental/physiology

(all 12)

PubMed

34568948 Full text @ Development

Abstract

During early vertebrate heart development the heart transitions from a linear tube to a complex asymmetric structure, a morphogenetic process which occurs simultaneously with growth of the heart. Cardiac growth during early heart morphogenesis is driven by deployment of cells from the Second Heart Field (SHF) into both poles of the heart. Laminin is a core component of the extracellular matrix (ECM), and although mutations in laminin subunits are linked with cardiac abnormalities, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified tissue-specific expression of laminin genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis. Analysis of heart development in lamb1a zebrafish mutant embryos reveals mild morphogenetic defects and progressive cardiomegaly, and that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition. lamb1a mutants exhibit hallmarks of altered haemodynamics, and blocking cardiac contractility in lamb1a mutants rescues heart size and atrial SHF addition. Together this suggests that laminin mediates interactions between SHF deployment and cardiac biomechanics during heart development and growth in the developing embryo.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
aldh1a2	lamb1a^sh590/sh590	standard conditions	Long-pec		endocardium	ISH	Fig. 7
aldh1a2	lamb1a^sh590/sh590 + MO1-tnnt2a + MO4-tp53	standard conditions	Long-pec		endocardium	ISH	Fig. 7
aldh1a2	lamb1a^sh590/sh590 + MO4-tp53	standard conditions	Long-pec		endocardium	ISH	Fig. 7
aldh1a2	lamb1a^sh590/+	standard conditions	Long-pec	Not Detected	endocardium	ISH	Fig. 7
aldh1a2	lamb1a^sh590/+ + MO1-tnnt2a + MO4-tp53	standard conditions	Long-pec	Not Detected	endocardium	ISH	Fig. 7
aldh1a2	lamb1a^sh590/+ + MO4-tp53	standard conditions	Long-pec	Not Detected	endocardium	ISH	Fig. 7
DsRed2	lamb1a^sh590/sh590; f2Tg	standard conditions	Protruding-mouth		atrium cell	IFL	Fig. 3
DsRed2	lamb1a^sh590/sh590; f2Tg	standard conditions	Long-pec		atrium cell	IFL	Fig. 3
DsRed2	lamb1a^sh590/sh590; f2Tg	standard conditions	Prim-15		presumptive atrium heart tube cell	IFL	Fig. 3
DsRed2	lamb1a^sh590/sh590; f2Tg; twu34Tg	standard conditions	Long-pec		atrial endocardium	IFL	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + CRISPR1-lamc1 + CRISPR2-lamc1	standard conditions	Prim-15	heart tube myl7 expression decreased amount, abnormal	Fig. 2
AB + CRISPR1-lamc1 + CRISPR2-lamc1	standard conditions	Long-pec	heart myl7 expression spatial pattern, abnormal	Fig. 2
AB + CRISPR1-lamc1 + CRISPR2-lamc1	standard conditions	Protruding-mouth	heart myl7 expression increased amount, abnormal	Fig. 2
AB + CRISPR1-lamc1 + CRISPR2-lamc1	standard conditions	Protruding-mouth	heart myl7 expression spatial pattern, abnormal	Fig. 2
lamb1a^sh590/+ + MO1-tnnt2a + MO4-tp53	standard conditions	Prim-15	atrial endocardium lamb1b expression decreased amount, abnormal	Fig. 5
lamb1a^sh590/+ + MO1-tnnt2a + MO4-tp53	standard conditions	Prim-15	endocardium klf2a expression decreased amount, abnormal	Fig. 5
lamb1a^sh590/+ + MO1-tnnt2a + MO4-tp53	standard conditions	Prim-15	ventricular endocardium lamb1b expression decreased amount, abnormal	Fig. 5
lamb1a^sh590/+; f2Tg; twu34Tg	standard conditions	Long-pec	regulation of secondary heart field cardioblast proliferation normal process quality, normal	Fig. 4
lamb1a^sh590/+; f2Tg; twu34Tg	standard conditions	Long-pec	regulation of secondary heart field cardioblast proliferation normal process quality, normal	Fig. 6
lamb1a^sh590/+; f2Tg; twu34Tg + MO1-tnnt2a + MO4-tp53	standard conditions	Long-pec	regulation of secondary heart field cardioblast proliferation normal process quality, normal	Fig. 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
f2Tg	Tg(-5.1myl7:DsRed2-NLS)	Transgenic Insertion
s974Tg	Tg(myl7:LIFEACT-GFP)	Transgenic Insertion
sa379		Point Mutation	lamc1
sh587		Small Deletion	lamb1b
sh588		Small Deletion	lamb1b
sh589		Small Deletion	lamb1a
sh590		Small Deletion	lamb1a
tj229a		Unknown	lamb1a
twu34Tg	Tg(myl7:EGFP)	Transgenic Insertion

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
gata1a	MO1-gata1a	MRPHLNO
lamb1a	CRISPR1-lamb1a	CRISPR
lamb1b	CRISPR6-lamb1b	CRISPR
lamb1b	CRISPR5-lamb1b	CRISPR
lamb2	CRISPR6-lamb2	CRISPR
lamb2	CRISPR3-lamb2	CRISPR
lamb2	CRISPR4-lamb2	CRISPR
lamb2	CRISPR5-lamb2	CRISPR
lamc1	CRISPR1-lamc1	CRISPR
lamc1	CRISPR2-lamc1	CRISPR

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Fish

Fish
AB
AB + CRISPR1-lamc1 + CRISPR2-lamc1
f2Tg
f2Tg/f2Tg
lamb1a^sh589/sh589
lamb1a^sh590/sh590
lamb1a^sh590/sh590; f2Tg
lamb1a^sh590/sh590; f2Tg; s974Tg
lamb1a^sh590/sh590; f2Tg; twu34Tg
lamb1a^sh590/sh590; f2Tg; twu34Tg + MO1-tnnt2a

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab9-h3	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Derrick et al., 2021 ZDB-PUB-210928-13 PMID:34568948

Lamb1a regulates atrial growth by limiting second heart field addition during zebrafish heart development

Derrick et al., 2021

ZDB-PUB-210928-13
PMID:34568948