Serum Response Factor Is Required for Sprouting Angiogenesis and Vascular Integrity
15/09/2008
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.
Developmental Cell, Vol 15, 448-461, 16 September 2008
Developmental Cell, Vol 15, 448-461, 16 September 2008
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