title: FoxO1 is required in endothelial but not myocardial cell lineages during cardiovascular development.
abstract: BACKGROUND
  The forkhead transcription factor FoxO1 is involved in cell cycle regulation during cardiovascular development. Systemic loss of FoxO1 results in lethality at embryonic day 10.5 with severe cardiovascular defects; however, the cell-type-specific requirements for FoxO1 in cardiovascular development are unknown. Here we examine the role of FoxO1 using a conditional loss of function approach.
  
  
  RESULTS
  Loss of FoxO1 in differentiated cardiac myocytes has no apparent effect on cardiovascular development. In contrast, endothelial-specific FoxO1 deficiency in Tie2Cre;FoxO1(fl/fl) embryos results in lethality at E10.5, which recapitulates the FoxO1-null phenotype. Tie2Cre;FoxO1(fl/fl) embryos have an intact differentiated endothelium, but display defective remodeling of vasculature. Additional effects on heart development include reduced myocardial trabeculation, which is likely secondary to the endothelial abnormalities, and hypoplasia of endocardial cushions.
  
  
  CONCLUSIONS
  The phenotype of Tie2Cre;FoxO1(fl/fl) mutant embryos demonstrates that FoxO1 is required specifically in endothelial cells to regulate formation of the heart and vasculature during development.
authors.affiliation: Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: Arunima
authors.initials: A
authors.lastname: Sengupta
authors.forename: Santanu
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Jihye
authors.initials: J
authors.lastname: Paik
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Yutzey
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Evans-Anderson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D004730:Endothelium, Vascular / Q000196:embryology* / Q000502:physiology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology* / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D009928:Organ Specificity
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse