First published online September 12, 2006
Development 133, 1906e (2006)
© The Company of Biologists Limited
MAN1y interactions shape vascular development
Although the function of some inner nuclear membrane proteins is known, the
function of others - including Man1 - remains unclear. Man1 negatively
regulates Tgfß signalling by interacting with receptor-associated Smads
in cultured cells. But what is its role in vivo? On
p. 3919, Ishimura and
colleagues propose that Man1 regulates angiogenesis during mouse embryogenesis
by interacting with Smads. Their findings show that embryos in which the
Smad-interaction domain of Man1 is deleted die at midgestation, owing
to defects in their embryonic vasculature. They report that increased Smad2/3
signalling and Tgfß1 expression in these Man1-deficient embryos
cause increased extracellular matrix (ECM) deposition, as is also seen in
people with MAN1 mutations. This increased ECM deposition probably
inhibits endothelial cell proliferation and migration; the recruitment of
smooth muscle cells to the vascular wall is also disturbed. Together, these
results suggest that Man1 regulates embryonic vascular remodelling by
interacting with receptor-associated Smads at the inner nuclear membrane to
ultimately modulate Tgfß signalling.
Related articles in Development:
- Man1, an inner nuclear membrane protein, regulates vascular remodeling by modulating transforming growth factor ß signaling
- Akihiko Ishimura, Jennifer K. Ng, Masanori Taira, Stephen G. Young, and Shin-Ichi Osada
Development 2006 133: 3919-3928.
[Abstract]
[Full Text]
