The fully linked HTML version of this article has now been published.
Development ePress online publication date 19 Sep 2007
doi: 10.1242/dev.004432
Research article: Development and Disease
Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4
Jeanette Astorga
and
Peter Carlsson*
* Author for correspondence (e-mail: peter.carlsson{at}cmb.gu.se)
The first vasculature of the developing vertebrate embryo forms by assembly of endothelial cells into simple tubes from clusters of mesodermal angioblasts. Maturation of this vasculature involves remodeling, pruning and investment with mural cells. Hedgehog proteins are part of the instructive endodermal signal that triggers the assembly of the first primitive vessels in the mesoderm. We used a combination of genetic and in vitro culture methods to investigate the role of hedgehogs and their targets in murine extraembryonic vasculogenesis. We show that Bmps, in particular Bmp4, are crucial for vascular tube formation, that Bmp4 expression in extraembryonic tissues requires the forkhead transcription factor Foxf1 and that the role of hedgehog proteins in this process is to activate Foxf1 expression in the mesoderm. We show in the allantois that genetic disruption of hedgehog signaling (Smo-/-) has no effect on Foxf1 expression, and neither Bmp4 expression nor vasculogenesis are disturbed. By contrast, targeted inactivation of Foxf1 leads to loss of allantoic Bmp4 and vasculature. In vitro, the avascular Foxf1-/- phenotype can be rescued by exogenous Bmp4, and vasculogenesis in wild-type tissue can be blocked by the Bmp antagonist noggin. Hedgehogs are required for activation of Foxf1, Bmp4 expression and vasculogenesis in the yolk sac. However, vasculogenesis in Smo-/- yolk sacs can be rescued by exogenous Bmp4, consistent with the notion that the role of hedgehog signaling in primary vascular tube formation is as an activator of Bmp4, via Foxf1.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Gao, G. Yang, T. Weng, J. Du, X. Wang, J. Zhou, S. Wang, and X. Yang
Disruption of Smad4 in Odontoblasts Causes Multiple Keratocystic Odontogenic Tumors and Tooth Malformation in Mice
Mol. Cell. Biol.,
November 1, 2009;
29(21):
5941 - 5951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Peeters, K. Ottersbach, K. Bollerot, C. Orelio, M. de Bruijn, M. Wijgerde, and E. Dzierzak
Ventral embryonic tissues and Hedgehog proteins induce early AGM hematopoietic stem cell development
Development,
August 1, 2009;
136(15):
2613 - 2621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Kelly and K. K. Hirschi
Signaling Hierarchy Regulating Human Endothelial Cell Development
Arterioscler Thromb Vasc Biol,
May 1, 2009;
29(5):
718 - 724.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Swift and B. M. Weinstein
Arterial-Venous Specification During Development
Circ. Res.,
March 13, 2009;
104(5):
576 - 588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. B. Madison, L. B. McKenna, D. Dolson, D. J. Epstein, and K. H. Kaestner
FoxF1 and FoxL1 Link Hedgehog Signaling and the Control of Epithelial Proliferation in the Developing Stomach and Intestine
J. Biol. Chem.,
February 27, 2009;
284(9):
5936 - 5944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Varjosalo and J. Taipale
Hedgehog: functions and mechanisms
Genes & Dev.,
September 15, 2008;
22(18):
2454 - 2472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Song, L. Coleman, J. Shi, H. Beppu, K. Sato, K. Walsh, J. Loscalzo, and Y.-Y. Zhang
Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice
Am J Physiol Heart Circ Physiol,
August 1, 2008;
295(2):
H677 - H690.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2007
