Faculty Collaboration Database

Serum response factor is required for cell contact maintenance but dispensable for proliferation in visceral yolk sac endothelium. BMC Dev Biol 2011 Mar 14;11:18

Date

03/16/2011

Pubmed ID

21401944

Pubmed Central ID

PMC3065428

DOI

10.1186/1471-213X-11-18

Scopus ID

2-s2.0-79952515931 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

BACKGROUND: Endothelial-specific knockout of the transcription factor serum response factor (SRF) results in embryonic lethality by mid-gestation. The associated phenotype exhibits vascular failure in embryos as well as visceral yolk sac (VYS) tissues. Previous data suggest that this vascular failure is caused by alterations in cell-cell and cell-matrix contacts. In the current study, we sought to more carefully address the role of SRF in endothelial function and cell contact interactions in VYS tissues.

RESULTS: Tie2-Cre recombinase-mediated knockout of SRF expression resulted in loss of detectable SRF from VYS mesoderm by E12.5. This loss was accompanied by decreased expression of smooth muscle alpha-actin as well as vascular endothelial cadherin and claudin 5, endothelial-specific components of adherens and tight junctions, respectively. Focal adhesion (FA) integrins alpha5 and beta1 were largely unchanged in contrast to loss of the FA-associated molecule vinculin. The integrin binding partner fibronectin-1 was also profoundly decreased in the extracellular matrix, indicating another aspect of impaired adhesive function and integrin signaling. Additionally, cells in SRF-null VYS mesoderm failed to reduce proliferation, suggesting not only that integrin-mediated contact inhibition is impaired but also that SRF protein is not required for proliferation in these cells.

CONCLUSIONS: Our data support a model in which SRF is critical in maintaining functional cell-cell and cell-matrix adhesion in endothelial cells. Furthermore, we provide evidence that supports a model in which loss of SRF protein results in a sustained proliferation defect due in part to failed integrin signaling.

Author List

Holtz ML, Misra RP

Author

Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Actins
Animals
Antigens, CD
Blood Vessels
Cadherins
Cell Adhesion
Cell Proliferation
Cell-Matrix Junctions
Claudin-5
Embryo, Mammalian
Endothelial Cells
Endothelium, Vascular
Fibronectins
Gene Expression Regulation, Developmental
Gene Knockout Techniques
Integrin alpha5
Integrin beta1
Membrane Proteins
Mesoderm
Mice
Mice, Transgenic
Polymerase Chain Reaction
Receptor, TIE-2
Serum Response Factor
Signal Transduction
Yolk Sac