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Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box m1 transcription factor
Author(s) -
Ramakrishna Sneha,
Kim IlMan,
Petrovic Vladimir,
Malin Dmitriy,
Wang IChing,
Kalin Tanya V.,
Meliton Lucille,
Zhao YouYang,
Ackerson Timothy,
Qin Yimin,
Malik Asrar B.,
Costa Robert H.,
Kalinichenko Vladimir V.
Publication year - 2007
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.21113
Subject(s) - biology , foxm1 , transcription factor , microbiology and biotechnology , mitosis , promoter , gene expression , cancer research , gene , genetics
The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 −/− mouse line to demonstrate that Foxm1‐deletion causes ventricular hypoplasia and diminished DNA replication and mitosis in developing cardiomyocytes. Proliferation defects in Foxm1 −/− hearts were associated with a reduced expression of Cdk1‐activator Cdc25B phosphatase and NFATc3 transcription factor, and with abnormal nuclear accumulation of the Cdk‐inhibitor p21 Cip1 protein. Depletion of Foxm1 levels by siRNA caused altered expression of these genes in cultured HL‐1 cardiomyocytes. Endothelial‐specific deletion of the Foxm1 fl/fl allele in Tie2‐Cre Foxm1 fl/fl embryos did not influence heart development and cardiomyocyte proliferation. Foxm1 protein binds to the −9,259/−9,288‐bp region of the endogenous mouse NFATc3 promoter, indicating that Foxm1 is a transcriptional activator of the NFATc3 gene. Foxm1 regulates expression of genes essential for the proliferation of cardiomyocytes during heart development. Developmental Dynamics 236:1000–1013, 2007. © 2007 Wiley‐Liss, Inc.