The Lack of ADAM17 Activity during Embryonic Development Causes Hemorrhage and Impairs Vessel Formation

By M. Canault, Kaan Certel, Daphne Schatzberg, D. Wagner, R. Hynes. 2010

32 citations recorded by the source corpus.

Background ADAM17/TACE activity is important during embryonic development. We wished to investigate possible roles of this metalloprotease, focusing on vascular development. Methodology/Principal Findings Mice mutant in the enzymatic activity of ADAM17 were examined at various stages of embryonic development for vascular pattern and integrity using markers for vessel wall cells. We observed hemorrhage and edema starting at embryonic day E14.5 and becoming more severe as development proceeded; prior to embryonic day E14.5, embryos appeared normal. Staining for PECAM-1/CD31 revealed abnormalities in the patterns of branching of the embryonic vasculature at E14.5. Conclusions/Significance These abnormalities preceded association of pericytes or monocyte/macrophage cells with the affected vessels and, therefore, presumably arise from defects in endothelial function consequent upon failure of ADAM17 to cleave one or more substrates involved in vascular development, such as Notch, Delta, VEGFR2 or JAM-A. Our study demonstrates a role for ADAM17 in modulating embryonic vessel development and function.

Subfields: Molecular Biology, Oncology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. A. Armulik
2. G. Genové
3. S. Zhong
4. E. Andersson
5. R. Khalil
6. Rickard Sandberg
7. U. Lendahl
8. C. Betsholtz

In Oncology

1. S. Zhong
2. R. Khalil
3. C. Iadecola

Citations in the corpus

• A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “Because of its wide involvement in development, ADAM-17−/− embryos die perinatally [85], supporting its essential role in embryonic development [86].”
• Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. (2011, background): “When and how do pericytes come into play in BBB development? Previous review literature discusses the idea that pericytes regulate the BBB at the level of endothelial junctions (Abbott et al., 2010, 2006; Cardoso et al., 2010; Lai and Kuo, 2005).”
• Notch signaling: simplicity in design, versatility in function (2011, background): “Interestingly, different ADAMs have been implicated in this cleavage event (Brou et al., 2000; Canault et al., 2010; Tian et al., 2008; Tousseyn et al., 2009; van Tetering et al., 2009), and a recent report indicates that specific ADAM proteases may cleave Notch specifically in a liganddependent or…”