PUBLICATION

Mef2c factors are required for early but not late addition of cardiomyocytes to the ventricle

Authors
Kula-Alwar, D., Marber, M.S., Hughes, S.M., Hinits, Y.
ID
ZDB-PUB-201128-8
Date
2020
Source
Developmental Biology   470: 95-107 (Journal)
Registered Authors
Hinits, Yaniv, Hughes, Simon M.
Keywords
Cardiomyocyte, Growth, Second heart field, Zebrafish, mef2c
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Heart/embryology*
  • Heart Ventricles/embryology*
  • Homeobox Protein Nkx-2.5/genetics
  • Homeobox Protein Nkx-2.5/metabolism
  • Latent TGF-beta Binding Proteins/genetics
  • Latent TGF-beta Binding Proteins/metabolism
  • MEF2 Transcription Factors/genetics
  • MEF2 Transcription Factors/metabolism*
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism*
  • Mutation
  • Myocytes, Cardiac/physiology*
  • Organ Size
  • Organogenesis
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33245870 Full text @ Dev. Biol.
Abstract
During heart formation, the heart grows and undergoes dramatic morphogenesis to achieve efficient embryonic function. Both in fish and amniotes, much of the growth occurring after initial heart tube formation arises from second heart field (SHF)-derived progenitor cell addition to the arterial pole, allowing chamber formation. In zebrafish, this process has been extensively studied during embryonic life, but it is unclear how larval cardiac growth occurs beyond 3 days post-fertilisation (dpf). By quantifying zebrafish myocardial growth using live imaging of GFP-labelled myocardium we show that the heart grows extensively between 3 and 5 dpf. Using methods to assess cell division, cellular development timing assay and Kaede photoconversion, we demonstrate that proliferation, CM addition, and hypertrophy contribute to ventricle growth. Mechanistically, we show that reduction in Mef2c activity (mef2ca+/-;mef2cb-/-), downstream or in parallel with Nkx2.5 and upstream of Ltbp3, prevents some CM addition and differentiation, resulting in a significantly smaller ventricle by 3 dpf. After 3 dpf, however, CM addition in mef2ca+/-;mef2cb-/- mutants recovers to a normal pace, and the heart size gap between mutants and their siblings diminishes into adulthood. Thus, as in mice, there is an early time window when SHF contribution to the myocardium is particularly sensitive to loss of Mef2c activity.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes