Expression of Foxm1 Transcription Factor in Cardiomyocytes Is Required for Myocardial Development
作者： Craig Bolte , Yufang Zhang , I-Ching Wang , Tanya V. Kalin , Jeffrey D. Molkentin
DOI: 10.1371/JOURNAL.PONE.0022217
关键词:
摘要: Forkhead Box M1 (Foxm1) is a transcription factor essential for organ morphogenesis and development of various cancers. Although complete deletion Foxm1 in Foxm1−/− mice caused embryonic lethality due to severe abnormalities multiple systems, requirements cardiomyocytes remain be determined. This study was designed elucidate the cardiomyocyte-autonomous role signaling heart development. We generated new mouse model which specifically deleted from (Nkx2.5-Cre/Foxm1fl/f mice). Deletion sufficient disrupt induce late gestation. Nkx2.5-Cre/Foxm1fl/fl hearts were dilated with thinning ventricular walls interventricular septum, as well disorganization myocardium culminated cardiac fibrosis decreased capillary density. Cardiomyocyte proliferation diminished owing altered expression cell cycle regulatory genes, such Cdc25B, Cyclin B1, Plk-1, nMyc p21cip1. In addition, deficient displayed reduced CaMKIIδ, Hey2 myocardin, are critical mediators function myocardial growth. Our results indicate that proper required cardiomyocyte
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