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Cooperation between Vezf1 and RhoB during vascular development
Author(s) -
Stuhlmann Heidi,
Benjamin Laura,
Victor Andrea,
Ocaya Pauline
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.635.2
Subject(s) - rhob , lymphangiogenesis , lymphatic system , biology , haploinsufficiency , hypervascularity , phenotype , angiogenesis , pathology , lymphatic vessel , cancer research , microbiology and biotechnology , immunology , medicine , rhoa , genetics , metastasis , cancer , gene , signal transduction
Vascular endothelial zinc finger 1 ( Vezf1 ) encodes a zinc finger transcription factor that is essential for developmental angiogenesis and lymphangiogenesis. Vezf1 −/− embryos show vascular remodeling defects, loss of vascular integrity, internal bleeding and embryonic death. Haploinsufficiency is observed in 20% of Vezf1 +/− embryos, resulting in lymphatic hypervascularity, edema and hemorrhaging (Kuhnert et al Dev.Biol.2005) . Recent studies suggested that Vezf1 might functionally interact with Rho GTPases. We studied cooperation between Vezf1 and RhoB during vascular development by generating embryos with compound Vezf1;RhoB null alleles. Strikingly, loss of RhoB exacerbates the phenotypes associated with loss of one Vezf1 allele. The phenotypes include: 1) enlarged head vessels 2) vascular anomalies at multiple sites in the head, hypervascularity, and hemorrhaging of internal organs, and 3) hypervascular lymphatic phenotype with blood‐filled vessels in the neck. These structures display similarities with human vascular and lymphatic anomalies. Thus, the results suggest that Vezf1 and RhoB cooperate in vivo, and indicate their potential role in human vascular pathologies.