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Science 294 (5542): 559-563

Copyright © 2001 by the American Association for the Advancement of Science

Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function

Kunio Matsumoto,12* Hideyuki Yoshitomi,1* Janet Rossant,13 Kenneth S. Zaret1dagger

The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.

1 Cell and Developmental Biology Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
2 Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
3 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5T 1K5, Canada.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: zaret{at}

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