Vegfd, a member of the VEGF family, is implicated in angiogenesis and lymphangiogenesis [2]. It is also critical for maintaining the structural integrity of mature dendritic trees in neurons [3]. In the context of vascular development, Vegfd signaling pathways interact with factors like Sox18, modulating arteriovenous differentiation [5].

In myofibroma, a novel COL4A1-VEGFD gene fusion was identified, leading to VEGFD production under the control of the COL4A1 gene promoter [1]. In lung adenocarcinoma, S-nitrosylation-mediated suppression of VEGFD expression promotes tumorigenesis [2]. In zebrafish, vegfd mutants display defects in facial lymphangiogenesis, and Vegfd cooperates with Vegfc to control lymphangiogenesis and also has compensatory roles in blood vessel angiogenesis [4]. Sox18/Vegfd double knockout mice show dramatic vascular development defects, suggesting Vegfd modulates SOX18-mediated transcription in vascular endothelial cells [5].

In conclusion, Vegfd plays essential roles in angiogenesis, lymphangiogenesis, and the maintenance of dendritic structures. Gene knockout models, such as the Sox18/Vegfd double knockout mice, have revealed its significance in vascular development. Its dysregulation is associated with diseases like myofibroma and lung adenocarcinoma, highlighting its potential as a therapeutic target in these disease areas.