Barrier Overcome to Growing Organs from Stem Cells by Proving Control of Embryonic Development in Fish

Scientists at the University of Virginia School of Medicine have overcome one of the greatest challenges in biology and taken a major step toward being able to grow whole organs and tissues from stem cells. By manipulating the appropriate signaling, the U.Va. researchers have turned embryonic stem cells into a fish embryo, essentially controlling embryonic development.

The research will have dramatic impact on the future use of stem cells to better the human condition, providing a framework for future studies in the field of regenerative medicine aimed at constructing tissues and organs from populations of cultured pluripotent cells.

The researchers were able to identify the signals sufficient for starting the cascade of molecular and cellular processes that lead to a fully developed fish embryo. With this study came an answer to the longstanding question of how few signals can initiate the processes of development: amazingly, only two.

The study has shed light on the important roles these two signals play for the formation of organs and full development of a zebrafish embryo. Moreover, the Thisses are now able to direct embryonic development and formation of tissues and organs by controlling signal locations and concentrations.

Their next steps will be to attempt to reproduce their findings using mice. They expect molecular and cellular mechanisms will be extremely similar in mice and other mammals – including humans.

U.Va. scientists Bernard and Chris Thisse have created a zebrafish embryo by instructing stem cells.

Science – Construction of a Vertebrate Embryo from Two Opposing Morphogen Gradients

ABSTRACT

Development of vertebrate embryos involves tightly regulated molecular and cellular processes that progressively instruct proliferating embryonic cells about their identity and behavior. Whereas numerous gene activities have been found to be essential during early embryogenesis, little is known about the minimal conditions and factors that would be sufficient to instruct pluripotent cells to organize the embryo. Here, we show that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.

Science Editors Summary – Designer Embryo

Numerous signaling pathways have been implicated in controlling early vertebrate embryogenesis. P.-F. Xu et al identify the minimal set of factors necessary to get uncommitted cells to organize a complete embryo. Two opposing gradients of the growth factors Nodal and Bone Morphogenetic Protein were sufficient to instruct zebrafish embryonic pluripotent cells to organize a complete embryo, not only in vivo but also in vitro. These findings may provide guidance for regenerative medicine studies aimed at constructing tissues and organs in vitro from cultured pluripotent cells.

18 pages of supplemental material

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