title: The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development.
abstract: GATA and Friend of GATA (FOG) form a transcriptional complex that plays a key role in cardiovascular development in both fish and mammals. In the present study we demonstrate that the basic helix-loop-helix transcription factor Atonal homolog 8 (Atoh8) is required for development of the heart in fish but not in mice. Genetic studies reveal that Atoh8 interacts specifically with Gata4 and Fog1 during development of the heart and swim bladder in the fish. Biochemical studies reveal that ATOH8, GATA4, and FOG2 associate in a single complex in vitro. In contrast to fish, ATOH8-deficient mice exhibit normal cardiac development and loss of ATOH8 does not alter cardiac development in Gata4(+/-) mice. This species difference in the role of ATOH8 is explained in part by LacZ and GFP reporter alleles that reveal restriction of Atoh8 expression to atrial but not ventricular myocardium in the mouse. Our findings identify ATOH8 as a novel regulator of GATA-FOG function that is required for cardiac development in the fish but not the mouse. Whether ATOH8 modulates GATA-FOG function at other sites or in more subtle ways in mammals is not yet known.
authors.affiliation: Department of Medicine and Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Rawnsley
authors.forename: Jiping
authors.initials: J
authors.lastname: Xiao
authors.forename: John S
authors.initials: JS
authors.lastname: Lee
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Patricia
authors.initials: P
authors.lastname: Mericko-Ishizuka
authors.forename: Vinayak
authors.initials: V
authors.lastname: Kumar
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Arindam
authors.initials: A
authors.lastname: Basu
authors.forename: MinMin
authors.initials: M
authors.lastname: Lu
authors.forename: Francis C
authors.initials: FC
authors.lastname: Lynn
authors.forename: Michael
authors.initials: M
authors.lastname: Pack
authors.forename: Rosa
authors.initials: R
authors.lastname: Gasa
authors.forename: Mark L
authors.initials: ML
authors.lastname: Kahn
mesh_terms: D000400:Air Sacs / Q000196:embryology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006325:Heart Atria / Q000196:embryology; D006352:Heart Ventricles / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity / Q000502:physiology; D038081:Organogenesis / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; D050991:GATA4 Transcription Factor; D046912:Multiprotein Complexes; D014157:Transcription Factors; D029961:Zebrafish Proteins; C449163:Atoh8 protein, mouse; C484170:GATA4 protein, human; C525957:Gata4 protein, zebrafish; C492170:Zfpm2 protein, mouse
keywords: Cardiac Development; Development; Friend of Gata; Gata; Gene Knockout; Transcription Factors