TETs regulate proepicardial cell migration through extracellular matrix organization during zebrafish cardiogenesis Journal Article


Authors: Lan, Y.; Pan, H.; Li, C.; Banks, K. M.; Sam, J.; Ding, B.; Elemento, O.; Goll, M. G.; Evans, T.
Article Title: TETs regulate proepicardial cell migration through extracellular matrix organization during zebrafish cardiogenesis
Abstract: Lan et al. show that zebrafish larvae mutant for tet2 and tet3 fail to demethylate genes encoding Inhbaa (in endocardium) and Sox9b (in myocardium), leading to defects in ECM needed to form valves and to recruit epicardial progenitors onto the heart tube. © 2018 The Author(s) Ten-eleven translocation (Tet) enzymes (Tet1/2/3) mediate 5-methylcytosine (5mC) hydroxylation, which can facilitate DNA demethylation and thereby impact gene expression. Studied mostly for how mutant isoforms impact cancer, the normal roles for Tet enzymes during organogenesis are largely unknown. By analyzing compound mutant zebrafish, we discovered a requirement for Tet2/3 activity in the embryonic heart for recruitment of epicardial progenitors, associated with development of the atrial-ventricular canal (AVC). Through a combination of methylation, hydroxymethylation, and transcript profiling, the genes encoding the activin A subunit Inhbaa (in endocardium) and Sox9b (in myocardium) were implicated as demethylation targets of Tet2/3 and critical for organization of AVC-localized extracellular matrix (ECM), facilitating migration of epicardial progenitors onto the developing heart tube. This study elucidates essential DNA demethylation modifications that govern gene expression changes during cardiac development with striking temporal and lineage specificities, highlighting complex interactions in multiple cell populations during development of the vertebrate heart. © 2018 The Author(s)
Keywords: genetics; endocardium; heart development; dna demethylation
Journal Title: Cell Reports
Volume: 26
Issue: 3
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2019-01-15
Start Page: 720
End Page: 732.e4
Language: English
DOI: 10.1016/j.celrep.2018.12.076
PUBMED: 30650362
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Mary Grace Goll
    10 Goll
  2. Cheng Li
    4 Li