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Endoglin is required in Pax3-derived cells for embryonic blood vessel formation

Lookup NU author(s): Professor Helen ArthurORCiD


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Mutations in endoglin, a TGF beta/BMP coreceptor, are causal for hereditary hemorrhagic telangiectasia (HHT). Endoglin-null (Eng-/-) mouse embryos die at embryonic day (E)10.5-11.5 due to defects in angiogenesis. In part, this is due to an absence of vascular smooth muscle cell differentiation and vessel investment. Prior studies from our lab and others have shown the importance of endoglin expression in embryonic development in both endothelial cells and neural crest stem cells. These studies support the hypothesis that endoglin may play cell-autonomous roles in endothelial and vascular smooth muscle cell precursors. However, the requirement for endoglin in vascular cell precursors remains poorly defined. Our objective was to specifically delete endoglin in neural crest- and somite-derived Pax3-positive vascular precursors to understand the impact on somite progenitor cell contribution to embryonic vascular development. Pax3Cre mice were crossed with Eng+/- mice to obtain compound mutant PaX3(Cre/+);Eng+/- mice. These mice were then crossed with homozygous endoglin LoxP-mutated (Eng(LoxP/LoxP)) mice to conditionally delete the endoglin gene in specific lineages that contribute to endothelial and smooth muscle constituents of developing embryonic vessels. Pax3(Cre/+);Eng(LoxP/-) mice showed a variety of vascular defects at E10.5, and none of these mice survived past E12.5. Embryos analyzed at E10.5 showed malformations suggestive of misdirection of the intersomitic vessels. The dorsal aorta showed significant dilation with associated vascular smooth muscle cells exhibiting disorganization and enhanced expression of smooth muscle differentiation proteins, including smooth muscle actin. These results demonstrate a requirement for endoglin in descendants of Pax3-expressing vascular cell precursors, and thus provides new insight into the cellular basis underlying adult vascular diseases such as HHT. (C) 2015 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Young K, Krebs LT, Tweedie E, Conley B, Mancini M, Arthur HM, Liaw L, Gridley T, Vary CPH

Publication type: Article

Publication status: Published

Journal: Developmental Biology

Year: 2016

Volume: 409

Issue: 1

Pages: 95-105

Print publication date: 01/01/2016

Online publication date: 19/10/2015

Acceptance date: 15/10/2015

ISSN (print): 0012-1606

ISSN (electronic): 1095-564X

Publisher: Academic Press


DOI: 10.1016/j.ydbio.2015.10.019


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Funder referenceFunder name
Maine Medical Center
GRNT20460045American Heart Association
P20-RR-15555National Institutes of Health National Center for Research Resources