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FoxO1 is required in endothelial but not myocardial cell lineages during cardiovascular development
Author(s) -
Sengupta Arunima,
Chakraborty Santanu,
Paik Jihye,
Yutzey Katherine E.,
EvansAnderson Heather J.
Publication year - 2012
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23759
Subject(s) - foxo1 , biology , phenotype , medicine , heart development , endocrinology , transcription factor , embryo , endothelium , myocyte , heart failure , embryonic stem cell , microbiology and biotechnology , genetics , gene
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. Developmental Dynamics 241:803–813, 2012. © 2012 Wiley Periodicals, Inc.