RRC ID 76489
Author Kula-Alwar D, Marber MS, Hughes SM, Hinits Y.
Title Mef2c factors are required for early but not late addition of cardiomyocytes to the ventricle.
Journal 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.
Volume 470
Pages 95-107
Published 2021-2-1
DOI 10.1016/j.ydbio.2020.11.008
PII S0012-1606(20)30306-7
PMID 33245870
PMC PMC7819464
MeSH 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*
IF 2.896
Zebrafish UAS:RFP