Premium
Adam10 is essential for early embryonic cardiovascular development
Author(s) -
Zhang Chi,
Tian Lei,
Chi Congwu,
Wu Xiaohui,
Yang Xiao,
Han Min,
Xu Tian,
Zhuang Yuan,
Deng Kejing
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.22391
Subject(s) - biology , notch signaling pathway , adam10 , microbiology and biotechnology , notch proteins , embryonic stem cell , heart development , embryogenesis , gene , signal transduction , genetics , embryo , matrix metalloproteinase , metalloproteinase , disintegrin
Notch pathway has been demonstrated to regulate cardiovascular development. One important step in Notch pathway is the cleavage of Notch receptor, during which an intracellular fragment of Notch protein is released to activate downstream genes. It is still uncertain whether Adam10 , the mammalian homologue of Kuzbanian in Drosophila , is required to activate the Notch pathway during cardiovascular development. To further understand the physiological function of Adam10 in vascular and cardiac development, we generated mice lacking the Adam10 gene primarily in the endothelial compartment. We found that disruption of Adam10 in endothelial cells resulted in embryonic death after embryonic day 10.5 due to multiple cardiac and vascular defects similar to Notch1 mutants. We further showed that the expression of Notch target genes Snail and Bmp2 are impaired in Adam10 ‐deficient cardiac tissues. Finally, we provide experimental evidence to support that Adam10 functions in a cell autonomous manner during mammalian cardiac development. Developmental Dynamics 239:2594–2602, 2010. © 2010 Wiley‐Liss, Inc.