title: 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish.
abstract: Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5(+) cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yan
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shanhe
authors.initials: S
authors.lastname: Yu
authors.forename: Guixiang
authors.initials: G
authors.lastname: Ji
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000502:physiology; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism; D064251:Multifunctional Enzymes / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C586372:8-oxoguanine DNA glycosylase 1, zebrafish; D064251:Multifunctional Enzymes; D014157:Transcription Factors; D029961:Zebrafish Proteins; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Cardiac progenitor cells; DNA repair; Heart development; Ogg1; Oxidative DNA damage