Adam10 is essential for early embryonic cardiovascular development.
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.
Zhang
Chi
C
Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, Shanghai, China.
Tian
Lei
L
Chi
Congwu
C
Wu
Xiaohui
X
Yang
Xiao
X
Han
Min
M
Xu
Tian
T
Zhuang
Yuan
Y
Deng
Kejing
K
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002319:Cardiovascular System / Q000196:embryology*; D058750:Epithelial-Mesenchymal Transition; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051881:Receptor, Notch1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C000604451:sna protein, Drosophila; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse