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.

在斑马鱼中，脑淋巴内皮细胞（BLEC）对于脑膜血管生成和脑血管再生至关重要。尽管据报道表皮生长因子样结构域 7 (Egfl7) 可以作为促血管生成因子，但其在淋巴管生成中的作用仍不清楚。在这里，我们发现 Egfl7 在血液和淋巴内皮细胞中表达。我们生成了一个egfl7 ^cq180突变体，其外显子3中有13-bp缺失，导致Egfl7表达减少。 egfl7 ^cq180突变斑马鱼表现出 BLEC 双侧环状结构形成缺陷，但躯干和面部淋巴管发育不受影响。此外，虽然egfl7 ^cq180突变体表现出正常的BLEC谱系规范，但这些细胞的迁移和增殖受到损害。此外，我们确定整合素 αvβ3 是 Egfl7 的受体。 αvβ3 在 CVP 和萌芽的 BLEC 中表达，阻断该整合素可抑制 BLEC 双侧环样结构的形成。因此，本研究确定了 Egfl7 在 BLEC 发育中通过整合素 αvβ3 介导的作用。