Integrin-α5β1 is not required for mural cell functions during development of blood vessels but is required for lymphatic-blood vessel separation and lymphovenous valve formation
Name
Turner et al DEVEL. final Ms reduced.pdf
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Author(s)
Turner, Christopher J.
Badu-Nkansah, Kwabena
Crowley, Denise
van der Flier, Arjan
Hynes, Richard O.
Date Issued
May 2014
Journal
Developmental Biology
Publisher
Elsevier
Citation
Turner, Christopher J., Kwabena Badu-Nkansah, Denise Crowley, Arjan van der Flier, and Richard O. Hynes. “Integrin-Α5β1 Is Not Required for Mural Cell Functions During Development of Blood Vessels but Is Required for Lymphatic-Blood Vessel Separation and Lymphovenous Valve Formation.” Developmental Biology 392, no. 2 (August 2014): 381–392.
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Author's final manuscript
Abstract
Integrin α5β1 is essential for vascular development but it remains unclear precisely where and how it functions. Here, we report that deletion of the gene encoding the integrin-α5 subunit (Itga5) using the Pdgfrb-Cre transgenic mouse line, leads to oedema, haemorrhage and increased levels of embryonic lethality. Unexpectedly, these defects were not caused by loss of α5 from Pdgfrb-Cre expressing mural cells (pericytes and vascular smooth muscle cells), which wrap around the endothelium and stabilise blood vessels, nor by defects in the heart or great vessels, but were due to abnormal development of the lymphatic vasculature. Reminiscent of the pathologies seen in the human lymphatic malformation, fetal cystic hygroma, α5 mutants display defects both in the separation of their blood and lymphatic vasculature and in the formation of the lymphovenous valves. As a consequence, α5-deficient mice develop dilated, blood-filled lymphatic vessels and lymphatic capillaries that are ectopically covered with smooth muscle cells. Analysis of the expression of Pdgfrb during lymphatic development suggests that these defects probably arise from loss of α5β1 integrin in subsets of specialised Prox1+Pdgfrb+ venous endothelial cells that are essential for the separation of the jugular lymph sac from the cardinal vein and formation of the lymphovenous valve leaflets.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.ydbio.2014.05.006
