The fully linked HTML version of this article has now been published.
Development ePress online publication date 8 Apr 2004
doi: 10.1242/dev.01091
Research article: Development and disease
Extra-embryonic vasculature development is regulated by the transcription factor HAND1
Yuka Morikawa
and
Peter Cserjesi*
* Author for correspondence (e-mail: pcserj{at}lsuhsc.edu)
The basic helix-loop-helix (bHLH) transcription factor HAND1 (also called eHAND) is expressed in numerous tissues during development including the heart, limbs, neural crest derivatives and extra-embryonic membranes. To investigate the role of Hand1 during development, we generated a Hand1 knockout mouse. Hand1-null mice survived to the nine somite stage at which time they succumbed to numerous developmental defects. One striking defect in Hand1-null embryos was the accumulation of hematopoietic cells between the yolk sac and the amnion because of defects in the yolk sac vasculature. In Hand1-null yolk sacs, vasculogenesis occurs but vascular refinement was arrested. Analysis of angiogenic genes in extra-embryonic membranes showed that most are expressed at normal levels in Hand1-null embryos but several, including Vegf, Ang1 and ephrin B2, and gene components of the Notch pathway are upregulated. In the absence of Hand1 the expression of the bHLH factor Hand2 is also enhanced. Although HAND1 and HAND2 share many structural features, and Hand2 is required for vasculature development in yolk sacs, enhanced expression of Hand2 is insufficient to compensate for the loss of Hand1. The most striking aspect of the vascular defect in Hand1 mutant yolk sacs is the abnormal distribution of smooth muscle cells. During normal angiogenesis, vascular smooth muscle precursors are recruited to the peri-endothelial tissue before differentiation, however, in Hand1 null yolk sacs, smooth muscle cells are not recruited but differentiate in clusters distributed throughout the mesoderm. These data indicate that Hand1 is required for angiogenesis and vascular smooth muscle recruitment in the yolk sac.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Morikawa, A. Zehir, E. Maska, C. Deng, M. D. Schneider, Y. Mishina, and P. Cserjesi
BMP signaling regulates sympathetic nervous system development through Smad4-dependent and -independent pathways
Development,
November 1, 2009;
136(21):
3575 - 3584.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Morikawa and P. Cserjesi
Cardiac Neural Crest Expression of Hand2 Regulates Outflow and Second Heart Field Development
Circ. Res.,
December 5, 2008;
103(12):
1422 - 1429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Palmieri, P. Loi, G. Ptak, and L.D. Salda
REVIEW PAPER: A Review of the Pathology of Abnormal Placentae of Somatic Cell Nuclear Transfer Clone Pregnancies in Cattle, Sheep, and Mice
Vet. Pathol.,
November 1, 2008;
45(6):
865 - 880.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. French, E. E. Creemers, and M. D. Tallquist
Platelet-Derived Growth Factor Receptors Direct Vascular Development Independent of Vascular Smooth Muscle Cell Function
Mol. Cell. Biol.,
September 15, 2008;
28(18):
5646 - 5657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. D'Autreaux, Y. Morikawa, P. Cserjesi, and M. D. Gershon
Hand2 is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia
Development,
June 15, 2007;
134(12):
2237 - 2249.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hamik, B. Wang, and M. K. Jain
Transcriptional Regulators of Angiogenesis
Arterioscler Thromb Vasc Biol,
September 1, 2006;
26(9):
1936 - 1947.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Park, K. Lavine, Y. Mishina, C.-X. Deng, D. M. Ornitz, and K. Choi
Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation
Development,
September 1, 2006;
133(17):
3473 - 3484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. L. M. Herrera, L. R. B. Ponce, P. D. Bagamasbad, B. D. VanPelt, T. Didishvili, and N. Ruiz-Opazo
Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis
Physiol Genomics,
November 17, 2005;
23(3):
257 - 268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Armulik, A. Abramsson, and C. Betsholtz
Endothelial/Pericyte Interactions
Circ. Res.,
September 16, 2005;
97(6):
512 - 523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Morin, G. Pozzulo, L. Robitaille, J. Cross, and M. Nemer
MEF2-dependent Recruitment of the HAND1 Transcription Factor Results in Synergistic Activation of Target Promoters
J. Biol. Chem.,
September 16, 2005;
280(37):
32272 - 32278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kawai-Kowase, M. S. Kumar, M. H. Hoofnagle, T. Yoshida, and G. K. Owens
PIAS1 Activates the Expression of Smooth Muscle Cell Differentiation Marker Genes by Interacting with Serum Response Factor and Class I Basic Helix-Loop-Helix Proteins
Mol. Cell. Biol.,
September 15, 2005;
25(18):
8009 - 8023.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. C. Carvalho, L. Jonker, M.-J. Goumans, J. Larsson, P. Bouwman, S. Karlsson, P. t. Dijke, H. M. Arthur, and C. L. Mummery
Defective paracrine signalling by TGF{beta} in yolk sac vasculature of endoglin mutant mice: a paradigm for hereditary haemorrhagic telangiectasia
Development,
December 15, 2004;
131(24):
6237 - 6247.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2004
Gene