title: The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field.
abstract: The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window. Although heart tube elongation deficiencies lead to life-threatening congenital heart defects, the variables controlling the initiation, rate and duration of myocardial accretion remain obscure. Here, we demonstrate that the AP-1 transcription factor, Fos-like antigen 2 (Fosl2), potentiates the rate of myocardial accretion from the zebrafish SHF. fosl2 mutants initiate accretion appropriately, but cardiomyocyte production is sluggish, resulting in a ventricular deficit coupled with an accumulation of SHF progenitors. Surprisingly, mutant embryos eventually correct the myocardial deficit by extending the accretion window. Overexpression of Fosl2 also compromises production of SHF-derived ventricular cardiomyocytes, a phenotype that is consistent with precocious depletion of the progenitor pool. Our data implicate Fosl2 in promoting the progenitor to cardiomyocyte transition and uncover the existence of regulatory mechanisms to ensure appropriate SHF-mediated cardiomyocyte contribution irrespective of embryonic stage.
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Jahangiri
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michka
authors.initials: M
authors.lastname: Sharpe
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Novikov
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: González-Rosa
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Asya
authors.initials: A
authors.lastname: Borikova
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Nevis
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Noelle
authors.initials: N
authors.lastname: Paffett-Lugassy
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Adams
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Burcu
authors.initials: B
authors.lastname: Guner-Ataman
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA Harvard Stem Cell Institute, Cambridge, MA 02138, USA cburns6@partners.org gburns@cvrc.mgh.harvard.edu.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Burns
authors.affiliation: Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA Harvard Medical School, Boston, MA 02115, USA cburns6@partners.org gburns@cvrc.mgh.harvard.edu.
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Burns
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics; D051921:Fos-Related Antigen-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000235:genetics; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D020539:Sequence Analysis, Protein; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051921:Fos-Related Antigen-2; D018808:Transcription Factor AP-1; D029961:Zebrafish Proteins
keywords: AP-1; Cardiac development; Fosl2; Heart; Second heart field; Zebrafish