4.7 Article

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

期刊

DEVELOPMENT
卷 143, 期 4, 页码 589-594

出版社

COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.127670

关键词

Angiogenesis; Blood vessels; Tip cells; Development; Semaphorin 3A

资金

  1. Swiss National Science Foundation [310030B_147087]
  2. European Research Council [LYVICAM]
  3. Leducq Foundation Transatlantic Network of Excellence grant Lymph Vessels in Obesity and Cardiovascular Disease [11CVD03]
  4. Swiss National Science Foundation (SNF) [310030B_147087] Funding Source: Swiss National Science Foundation (SNF)

向作者/读者索取更多资源

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.

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