Serum response factor is required for sprouting angiogenesis and vascular integrity.
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 beta-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.
Franco
Claudio Areias
CA
UPMC Univ Paris 06, UMR 7079, Physiology and Physiopathology, 75005 Paris, France; CNRS, UMR 7079, 75005 Paris, France.
Mericskay
Mathias
M
UPMC Univ Paris 06, UMR 7079, Physiology and Physiopathology, 75005 Paris, France; CNRS, UMR 7079, 75005 Paris, France.
Parlakian
Ara
A
UPMC Univ Paris 06, UMR 7079, Physiology and Physiopathology, 75005 Paris, France; CNRS, UMR 7079, 75005 Paris, France.
Gary-Bobo
Guillaume
G
UPMC Univ Paris 06, UMR 7079, Physiology and Physiopathology, 75005 Paris, France; CNRS, UMR 7079, 75005 Paris, France.
Gao-Li
Jacqueline
J
UPMC Univ Paris 06, UMR 7079, Physiology and Physiopathology, 75005 Paris, France; CNRS, UMR 7079, 75005 Paris, France.
Paulin
Denise
D
CNRS, UMR 7079, 75005 Paris, France.
Gustafsson
Erika
E
Department of Experimental Pathology, Lund University, SE 221 85 Lund, Sweden.
Li
Zhenlin
Z
UPMC Univ Paris 06, UMR 7079, Physiology and Physiopathology, 75005 Paris, France; CNRS, UMR 7079, 75005 Paris, France. Electronic address: zhenli@ccr.jussieu.fr.
D000199:Actins / Q000378:metabolism; D000783:Aneurysm / Q000235:genetics / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001808:Blood Vessels / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology* / Q000473:pathology / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006470:Hemorrhage / Q000235:genetics / Q000401:mortality; D007365:Intercellular Junctions / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D042810:Receptor, TIE-1 / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D048049:Extracellular Signal-Regulated MAP Kinases; D005346:Fibroblast Growth Factors; D034741:RNA, Small Interfering; D042810:Receptor, TIE-1; D026362:Serum Response Factor; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C467480:vascular endothelial growth factor A, mouse