|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online August 24, 2007
doi: 10.1242/10.1242/dev.02883
1 Department of Molecular Physiology and Biophysics, Baylor College of Medicine,
Houston, TX 77030, USA.
2 Department of Chemical Engineering, California Institute of Technology,
Pasadena, CA 91125, USA.
3 Department of Medicine, School of Medicine, University of California-San
Diego, 9500 Gilman Drive, La Jolla, CA 92093-0641, USA.
4 Biological Imaging Center, Department of Biology, California Institute of
Technology, Pasadena, CA 91125, USA.
Author for correspondence (e-mail:
mdickins{at}bcm.tmc.edu)
Accepted 5 July 2007
The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a-/-). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sac.
Key words: Blood flow, Viscosity, Shear stress, Cardiovascular, Angiogenesis, eNOS (Nos3), Mlc2a (Myl7), Mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  S.-W. Jin and C. Patterson The Opening Act: Vasculogenesis and the Origins of Circulation Arterioscler. Thromb. Vasc. Biol., May 1, 2009; 29(5): 623 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Boulday, A. Blecon, N. Petit, F. Chareyre, L. A. Garcia, M. Niwa-Kawakita, M. Giovannini, and E. Tournier-Lasserve Tissue-specific conditional CCM2 knockout mice establish the essential role of endothelial CCM2 in angiogenesis: implications for human cerebral cavernous malformations Dis. Model. Mech., March 1, 2009; 2(3-4): 168 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Larrivee, C. Freitas, S. Suchting, I. Brunet, and A. Eichmann Guidance of Vascular Development: Lessons From the Nervous System Circ. Res., February 27, 2009; 104(4): 428 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. McKeown, R. B. Nowak, J. Moyer, M. A. Sussman, and V. M. Fowler Tropomodulin1 Is Required in the Heart but Not the Yolk Sac for Mouse Embryonic Development Circ. Res., November 21, 2008; 103(11): 1241 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Goldie, J. L. Lucitti, M. E. Dickinson, and K. K. Hirschi Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis Blood, October 15, 2008; 112(8): 3194 - 3204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Terada What Underlies Endothelial Shear Sensing? The Matrix, of Course Circ. Res., September 12, 2008; 103(6): 562 - 564. [Full Text] [PDF]
|
|
|
|
|
|
P. Patwari and R. T. Lee Mechanical Control of Tissue Morphogenesis Circ. Res., August 1, 2008; 103(3): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. V. Jones, L. Yuan, C. Breant, R. J. Watts, and A. Eichmann Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos Development, July 15, 2008; 135(14): 2479 - 2488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. He, H. Hu, R. Braren, S.-Y. Fong, A. Trumpp, T. R. Carlson, and R. A. Wang c-myc in the hematopoietic lineage is crucial for its angiogenic function in the mouse embryo Development, July 15, 2008; 135(14): 2467 - 2477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. Teichert, J. A. Scott, G. B. Robb, Y.-Q. Zhou, S.-N. Zhu, M. Lem, A. Keightley, B. M. Steer, A. C. Schuh, S. L. Adamson, et al. Endothelial Nitric Oxide Synthase Gene Expression During Murine Embryogenesis: Commencement of Expression in the Embryo Occurs With the Establishment of a Unidirectional Circulatory System Circ. Res., July 3, 2008; 103(1): 24 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. le Noble, C. Klein, A. Tintu, A. Pries, and I. Buschmann Neural guidance molecules, tip cells, and mechanical factors in vascular development Cardiovasc Res, May 1, 2008; 78(2): 232 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Lucitti, E. A. V. Jones, C. Huang, J. Chen, S. E. Fraser, and M. E. Dickinson Vascular remodeling of the mouse yolk sac requires hemodynamic force J. Cell Sci., September 15, 2007; 120(18): e1807 - e1807. [Full Text]
|
|
