Serum Response Factor Is Required for Sprouting Angiogenesis and Vascular Integrity

• Published in: Developmental cell Vol. 15; no. 3; pp. 448 - 461
• Main Authors: Franco, Claudio Areias, Mericskay, Mathias, Parlakian, Ara, Gary-Bobo, Guillaume, Gao-Li, Jacqueline, Paulin, Denise, Gustafsson, Erika, Li, Zhenlin
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.09.2008; Cell Press
• Subjects: Actins - metabolism; Aneurysm - genetics; Aneurysm - pathology; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Biological and medical sciences; Blood Vessels - anatomy & histology; Blood Vessels - metabolism; Blood Vessels - pathology; Cadherins - genetics; Cadherins - metabolism; Cancer and Oncology; Cancer och onkologi; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; CELLBIO; Clinical Medicine; DEVBIO; Embryo, Mammalian - anatomy & histology; Embryo, Mammalian - pathology; Embryo, Mammalian - physiology; Endothelial Cells - cytology; Endothelial Cells - physiology; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Profiling; Hemorrhage - genetics; Hemorrhage - mortality; Intercellular Junctions - metabolism; Intercellular Junctions - pathology; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular and cellular biology; Neovascularization, Physiologic - physiology; Receptor, TIE-1 - genetics; Receptor, TIE-1 - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Serum Response Factor - genetics; Serum Response Factor - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; CELLBIO; DEVBIO; Development; Angiogenesis; Serum
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2008.07.019

Serum response factor (SRF) is a transcription factor that controls the expression of cytoskeletal proteins and immediate early genes in different cell types. Here, we found that SRF expression is restricted to endothelial cells (ECs) of small vessels such as capillaries in the mouse embryo. EC-specific Srf deletion led to aneurysms and hemorrhages from 11.5 days of mouse development (E11.5) and lethality at E14.5. Mutant embryos presented a reduced capillary density and defects in EC migration, with fewer numbers of filopodia in tip cells and ECs showing defects in actin polymerization and intercellular junctions. We show that SRF is essential for the expression of VE-cadherin and β-actin in ECs both in vivo and in vitro. Moreover, knockdown of SRF in ECs impaired VEGF- and FGF-induced in vitro angiogenesis. Taken together, our results demonstrate that SRF plays an important role in sprouting angiogenesis and small vessel integrity in the mouse embryo.