PUBLICATION

In vivo analysis of cardiomyocyte proliferation during trabeculation.

Authors

Uribe, V., Ramadass, R., Dogra, D., Rasouli, S.J., Gunawan, F., Nakajima, H., Chiba, A., Reischauer, S., Mochizuki, N., Stainier, D.Y.R.

ID

ZDB-PUB-180801-3

Date

2018

Source

Development (Cambridge, England) 145(14): (Journal)

Registered Authors

Mochizuki, Naoki, Nakajima, Hiroyuki, Reischauer, Sven, Stainier, Didier

Keywords

Cardiomyocyte proliferation, Heart development, Sarcomere, Trabeculation

MeSH Terms

Cell Division
Zebrafish Proteins/metabolism
Zebrafish/genetics
Zebrafish/growth & development*
Transforming Growth Factor beta/metabolism
Ligands
Gene Expression Regulation, Developmental
Animals
Myocytes, Cardiac/cytology*
Myocytes, Cardiac/metabolism
Sarcomeres/metabolism
Organogenesis*
Signal Transduction
Cell Proliferation
Heart/growth & development
Cell Size
Cell Shape

(all 17)

PubMed

30061167 Full text @ Development

Abstract

Cardiomyocyte proliferation is crucial for cardiac growth, patterning and regeneration; however, few studies have investigated the behavior of dividing cardiomyocytes in vivo Here, we use time-lapse imaging of beating hearts in combination with the FUCCI system to monitor the behavior of proliferating cardiomyocytes in developing zebrafish. Confirming in vitro observations, sarcomere disassembly, as well as changes in cell shape and volume, precede cardiomyocyte cytokinesis. Notably, cardiomyocytes in zebrafish embryos and young larvae mostly divide parallel to the myocardial wall in both the compact and trabecular layers, and cardiomyocyte proliferation is more frequent in the trabecular layer. While analyzing known regulators of cardiomyocyte proliferation, we observed that the Nrg/ErbB2 and TGFβ signaling pathways differentially affect compact and trabecular layer cardiomyocytes, indicating that distinct mechanisms drive proliferation in these two layers. In summary, our data indicate that, in zebrafish, cardiomyocyte proliferation is essential for trabecular growth, but not initiation, and set the stage to further investigate the cellular and molecular mechanisms driving cardiomyocyte proliferation in vivo.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
BFP	bns141Tg; bns193Tg; ncv43Tg	control	Day 4	cardiac muscle cell membrane	IFL	Fig. 3
DsRedx	hsc4Tg	control	Day 5	cardiac muscle cell	IHC	Fig. 1
DsRedx	hsc4Tg	control	Day 4	cardiac muscle cell	IHC	Fig. 1
DsRedx	hsc4Tg	control	Day 5	trabecular layer cardiac muscle cell	IHC	Fig. 1
DsRedx	hsc4Tg; ncv43Tg	control	Day 4	cardiac muscle cell	IHC	Fig. 1
EGFP	bns7Tg; sd10Tg	control	Protruding-mouth	cardiac muscle cell Z disc	IFL	Fig. 3
GFP	sd11Tg; zf521Tg	control	Days 7-13	cardiac muscle cell	IFL	Fig. 4
GFP	sd11Tg; zf521Tg	chemical treatment by environment: PD 168393	Days 7-13	cardiac muscle cell	IFL	Fig. 4
mCherry	bns7Tg; sd10Tg	control	Protruding-mouth	cardiac muscle cell membrane	IFL	Fig. 3
mCherry	ncv43Tg; ncv68Tg	control	Day 4	cardiac muscle cell	IFL	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
bns140Tg	control	Long-pec	cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 4
bns140Tg	control	Protruding-mouth	cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 4
bns140Tg	control	Day 4	cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 4
bns146Tg	control	Day 4	cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 5
bns146Tg	control	Day 4	trabecular layer cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 5
bns146Tg	control	Day 5	cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 5
bns146Tg	control	Day 5	trabecular layer cardiac muscle cell proliferation increased occurrence, abnormal	Fig. 5
bns146Tg; sd11Tg	control	Days 7-13	heart trabecula formation increased rate, abnormal	Fig. 5
bns146Tg; sd11Tg	control	Days 7-13	trabecular layer cardiac muscle cell increased amount, abnormal	Fig. 5
mstnb^bns5/bns5; hsc4Tg	control	Day 5	cardiac muscle cell proliferation increased occurrence, abnormal	Fig. S8

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
bns5		Small Deletion	mstnb
bns7Tg	Tg(myl7:mCherry-CAAX)	Transgenic Insertion
bns140Tg	Tg(myl7:nrg2a-2A-Tomato)	Transgenic Insertion
bns141Tg	Tg(myl7:LIFEACT-Tomato)	Transgenic Insertion
bns146Tg	Tg(myl7:inhbaa-2A-Hsa.HISTH2BJ-EGFP)	Transgenic Insertion
bns193Tg	Tg(myl7:BFP-CAAX)	Transgenic Insertion
hsc4Tg	Tg(-0.8myl7:NLS-DsRedx)	Transgenic Insertion
ncv43Tg	Tg(myl7:mVenus-gmnn)	Transgenic Insertion
ncv68Tg	Tg2(myl7:mCherry-cdt1)	Transgenic Insertion
sd10Tg	Tg(myl7:actn3b-EGFP)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
bns7Tg; sd10Tg
bns140Tg
bns141Tg; bns193Tg; ncv43Tg
bns146Tg
bns146Tg; sd11Tg
hsc4Tg
hsc4Tg; ncv43Tg
mstnb^bns5/bns5; hsc4Tg
ncv43Tg
ncv43Tg; ncv68Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
BFP	EFG	BFP
DsRedx	EFG	DsRedx
EGFP	EFG	EGFP
GFP	EFG	GFP
mCherry	EFG	mCherry
mKate2	EFG	mKate2
Tomato	EFG	Tomato
Venus	EFG	Venus

Mapping

Uribe et al., 2018 ZDB-PUB-180801-3 PMID:30061167

In vivo analysis of cardiomyocyte proliferation during trabeculation.

Uribe et al., 2018

ZDB-PUB-180801-3
PMID:30061167