Endothelial SUR-8 acts in an ERK-independent pathway during atrioventricular cushion development.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yi, J; Chen, M; Wu, X; Yang, X; Xu, T; Zhuang, Y; Han, M; Xu, R

Published Date

  • July 2010

Published In

Volume / Issue

  • 239 / 7

Start / End Page

  • 2005 - 2013

PubMed ID

  • 20549726

Pubmed Central ID

  • PMC3138404

Electronic International Standard Serial Number (EISSN)

  • 1097-0177

Digital Object Identifier (DOI)

  • 10.1002/dvdy.22343


  • eng

Conference Location

  • United States