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Role of KLF2 in atrioventricular cushion development
Author(s) -
Haar Jack L.,
Lung Tina K.,
Chiplunkar Aditi R.,
Lloyd Joyce A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.830.10
Subject(s) - klf2 , mesenchymal stem cell , anatomy , microbiology and biotechnology , lymphangiogenesis , endothelium , biology , chemistry , transcription factor , endocrinology , gene , biochemistry , genetics , cancer , metastasis
Krüppel like factors (KLFs) are transcription factors with important roles in development. KLF2 KO mice die by embryonic day 14.5 (E14.5) and exhibit heart failure and hemorrhaging. KLF2 is expressed in multiple tissues including erythroid and endothelial cells. Our preliminary studies have shown that, KLF2 KO mice have abnormal development of the atrioventricular (AV) cushions of the heart. Light microscopy revealed that the E9.5 WT (n = 3) AV cushion is lined by a single layer of endothelial cells, with underlying mesenchymal cells. In E9.5 KLF2 KO mice (n = 3), there is 2‐fold increase of cells in the AV canal; these cells are not in a single layer. There was no significant difference in the mesenchymal cell count, but KLF2‐/‐ have a decreasing trend, compared to WT. Electron microscopy revealed that the WT AV canal is straight with no recesses; the endothelial cells lining the canal are squamous with no cell processes extending toward the lumen. In KLF2‐/‐ embryos, the canal is open with many recesses. It is lined by endothelial cells having numerous cytoplasmic processes extending toward the lumen. Based on these observations, the KLF2 gene is required for normal AV cushion development. The findings in this study further suggest the testable hypothesis that there may be abnormal endothelial to mesenchymal transformation in the AV cushions of KLF2 KO embryos. (Supported by NIH R01DK074694)