biostudies-literatureYi JHoward Hughes Medical InstituteNIGMS NIH HHS2005-13https://www.ebi.ac.uk/biostudies/studies/S-EPMC3138404biostudies-literatureUnknown239(7)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 atriDevelopmental dynamics : an official publication of the American Association of AnatomistsEndothelial SUR-8 acts in an ERK-independent pathway during atrioventricular cushion development.PMC3138404R01 GM047869Yi JYang XChen MHan MXu RXu TWu XZhuang YfalseEndothelial SUR-8 acts in an ERK-independent pathway during atrioventricular cushion development.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 atri2010-01-01T00:00:00Z2010 Jul2026-04-07T22:14:51.514Z2025-06-27T03:05:10.231ZS-EPMC31384042054972610.1002/dvdy.22343