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Endothelial SUR‐8 acts in an ERK‐independent pathway during atrioventricular cushion development
Author(s) -
Yi Jing,
Chen Muyun,
Wu Xiaohui,
Yang Xiao,
Xu Tian,
Zhuang Yuan,
Han Min,
Xu Rener
Publication year - 2010
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.22343
Subject(s) - mesenchyme , biology , mapk/erk pathway , microbiology and biotechnology , embryonic stem cell , atrioventricular canal , regulator , mutant , caenorhabditis elegans , heart development , embryonic heart , embryo , signal transduction , genetics , medicine , heart disease , gene
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 © 2010 Wiley‐Liss, Inc.