Development ePress online publication date 17 December 2003 Research article 361 Flow regulates arterial-venous differentiation in the chick embryo yolk sac Ferdinand le Noble1,2, Delphine Moyon2, Luc Pardanaud2, Li Yuan2, Valentin Djonov3, Robert Matthijsen1, Christiane Bréant2, Vincent Fleury4 and Anne Eichmann2,* 1Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands 2Inserm U36, Collège de France, 11, Place Marcelin Berthelot, 75005 Paris, France 3Department of Anatomy, University of Bern, Switzerland 4Department of Physics, Ecole Polytechnique, Palaiseau, France *Author for correspondence (e-mail:
[email protected]) Accepted 17 October 2003 Development 131, 361-375 Published by The Company of Biologists 2004 doi:10.1242/dev.00929 Summary Formation of the yolk sac vascular system and its growth of veins. Arterial-venous differentiation and connection to the embryonic circulation is crucial for patterning are controlled by hemodynamic forces, as shown embryo survival in both mammals and birds. Most mice by flow manipulation and in situ hybridization with arterial with mutations in genes involved in vascular development markers ephrinB2 and neuropilin 1, which show that die because of a failure to establish this circulatory loop. expression of both mRNAs is not genetically determined Surprisingly, formation of yolk sac arteries and veins has but plastic and regulated by flow. In vivo application of not been well described in the recent literature. Using time- ephrinB2 or EphB4 in the developing yolk sac failed to lapse video-microscopy, we have studied arterial-venous produce any morphological effects. By contrast, ephrinB2 differentiation in the yolk sac of chick embryos. and EphB4 application in the allantois of older embryos Immediately after the onset of perfusion, the yolk sac resulted in the rapid formation of arterial-venous shunts.