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Epidermal growth factor-like domain 7 drives brain lymphatic endothelial cell development through integrin αvβ3

Author

Listed:
  • Jingying Chen

    (Fudan University)

  • Jing Ding

    (Southwest University)

  • Yongyu Li

    (Southwest University)

  • Fujuan Feng

    (Southwest University)

  • Yuhang Xu

    (Southwest University)

  • Tao Wang

    (Southwest University)

  • Jianbo He

    (Southwest University)

  • Jing Cang

    (Fudan University)

  • Lingfei Luo

    (Fudan University
    Southwest University)

Abstract

In zebrafish, brain lymphatic endothelial cells (BLECs) are essential for meningeal angiogenesis and cerebrovascular regeneration. Although epidermal growth factor-like domain 7 (Egfl7) has been reported to act as a pro-angiogenic factor, its roles in lymphangiogenesis remain unclear. Here, we show that Egfl7 is expressed in both blood and lymphatic endothelial cells. We generate an egfl7 cq180 mutant with a 13-bp-deletion in exon 3 leading to reduced expression of Egfl7. The egfl7 cq180 mutant zebrafish exhibit defective formation of BLEC bilateral loop-like structures, although trunk and facial lymphatic development remains unaffected. Moreover, while the egfl7 cq180 mutant displays normal BLEC lineage specification, the migration and proliferation of these cells are impaired. Additionally, we identify integrin αvβ3 as the receptor for Egfl7. αvβ3 is expressed in the CVP and sprouting BLECs, and blocking this integrin inhibits the formation of BLEC bilateral loop-like structures. Thus, this study identifies a role for Egfl7 in BLEC development that is mediated through the integrin αvβ3.

Suggested Citation

  • Jingying Chen & Jing Ding & Yongyu Li & Fujuan Feng & Yuhang Xu & Tao Wang & Jianbo He & Jing Cang & Lingfei Luo, 2024. "Epidermal growth factor-like domain 7 drives brain lymphatic endothelial cell development through integrin αvβ3," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50389-8
    DOI: 10.1038/s41467-024-50389-8
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