Endothelial cell-derived semaphorin 3A inhibits filopodia formation by blood vascular tip cells.

Ochsenbein, Alexandra M; Karaman, Sinem; Proulx, Steven T; Berchtold, Michaela; Jurisic, Giorgia; Stoeckli, Esther T; Detmar, Michael (2016). Endothelial cell-derived semaphorin 3A inhibits filopodia formation by blood vascular tip cells. Development, 143(4), pp. 589-594. Company of Biologists Limited 10.1242/dev.127670

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Vascular endothelial growth factor (VEGF)-A is a well-known major chemoattractant driver of angiogenesis--the formation of new blood vessels from pre-existing ones. However, the repellent factors that fine-tune this angiogenic process remain poorly characterized. We investigated the expression and functional role of endothelial cell-derived semaphorin 3A (Sema3A) in retinal angiogenesis, using genetic mouse models. We found Sema3a mRNA expression in the ganglion cell layer and the presence of Sema3A protein on larger blood vessels and at the growing front of blood vessels in neonatal retinas. The Sema3A receptors neuropilin-1 and plexin-A1 were expressed by retinal blood vessels. To study the endothelial cell-specific role of Sema3A, we generated endothelial cell-specific Sema3A knockout mouse strains by constitutive or inducible vascular endothelial cadherin-Cre-mediated gene disruption. We found that in neonatal retinas of these mice, both the number and the length of tip cell filopodia were significantly increased and the leading edge growth pattern was irregular. Retinal explant experiments showed that recombinant Sema3A significantly decreased VEGF-A-induced filopodia formation. Endothelial cell-specific knockout of Sema3A had no impact on blood vessel density or skin vascular leakage in adult mice. These findings indicate that endothelial cell-derived Sema3A exerts repelling functions on VEGF-A-induced tip cell filopodia and that a lack of this signaling cannot be rescued by paracrine sources of Sema3A.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0950-1991

Publisher:

Company of Biologists Limited

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

21 Oct 2020 15:29

Last Modified:

21 Oct 2020 16:03

Publisher DOI:

10.1242/dev.127670

PubMed ID:

26884395

Uncontrolled Keywords:

Angiogenesis Blood vessels Development Semaphorin 3A Tip cells

BORIS DOI:

10.7892/boris.147215

URI:

https://boris.unibe.ch/id/eprint/147215

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