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PMID:18804439

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Citation

Franco, CA, Mericskay, M, Parlakian, A, Gary-Bobo, G, Gao-Li, J, Paulin, D, Gustafsson, E and Li, Z (2008) Serum response factor is required for sprouting angiogenesis and vascular integrity. Dev. Cell 15:448-61

Abstract

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.

Links

PubMed Online version:10.1016/j.devcel.2008.07.019

Keywords

Actins/metabolism; Aneurysm/genetics; Aneurysm/pathology; Animals; Antigens, CD/genetics; Antigens, CD/metabolism; Blood Vessels/anatomy & histology; Blood Vessels/metabolism; Blood Vessels/pathology; Cadherins/genetics; Cadherins/metabolism; 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; Gene Deletion; Gene Expression Profiling; Hemorrhage/genetics; Hemorrhage/mortality; Intercellular Junctions/metabolism; Intercellular Junctions/pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neovascularization, Physiologic/physiology; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Receptor, TIE-1/genetics; Receptor, TIE-1/metabolism; Serum Response Factor/genetics; Serum Response Factor/metabolism; Vascular Endothelial Growth Factor A/genetics; Vascular Endothelial Growth Factor A/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SRF

acts_upstream_of_or_within

GO:0030155: regulation of cell adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(EMAPA:16104)

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0002042: cell migration involved in sprouting angiogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:16104)
  • results_in_movement_of:(CL:0000071)

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0001569: branching involved in blood vessel morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:16104)

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000071)
  • occurs_in:(EMAPA:16104)

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0051491: positive regulation of filopodium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000071)
  • regulates_o_occurs_in:(EMAPA:16104)

Seeded From UniProt

complete


See also

References

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