Journal
DEVELOPMENTAL DYNAMICS
Volume 239, Issue 7, Pages 2005-2013Publisher
WILEY
DOI: 10.1002/dvdy.22343
Keywords
SUR-8; atrioventricular cushion; MAPK/ERK; congenital heart disease; endothelial-mesenchymal transformation (EMT)
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Funding
- Ministry of Science and Technology [2006CB806704, 2006CB806705, 2007AA022101]
- National Science Foundation of China [30871233]
- Chinese Ministry of Education [211]
- 985 projects
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SUR-8, a conserved leucine-rich repeats protein, was first identified as a positive regulator of Ras pathway in Caenorhabditis elegans. Biochemical studies indicated that SUR-8 interacts with Ras and Raf, leading to the elevated ERK activity. However, the physiological role of SUR-8 during mammalian development remains unclear. Here we found that germline deletion of SUR-8 in mice resulted in early embryonic lethality. Inactivated SUR-8 specifically in mouse endothelial cells (ECs) revealed that SUR-8 is essential for embryonic heart development. SUR-8 deficiency in ECs resulted in late embryonic lethality, and the mutant mice displayed multiple cardiac defects. The reduced endothelial-mesenchymal transformation (EMT) and the reduced mesenchyme proliferation phase were observed in the atrioventricular canal (AVC) within the mutant hearts, leading to the formation of hypoplastic endocardial cushions. However, ERK activation did not appear to be affected in mutant ECs, suggesting that SUR-8 may act in an ERK-independent pathway to regulate AVC development. Developmental Dynamics 239:2005-2013, 2010. (C) 2010 Wiley-Liss, Inc.
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