During metazoan development, groups of cells, often
from different germ layers, come together to form the individual organs.
As a paradigm to study organogenesis, we are focusing on the development
of the heart. The embryonic heart is a simple structure which consists
of two concentric epithelial tubes, the outer myocardial tube that
forms the muscular component of the heart, and the inner endocardial
tube that forms its endothelial lining.
We have elected to study heart development in the zebrafish, Danio
rerio, because it offers unique advantages as a vertebrate genetic
system and is also ideal for embryological studies. The zebrafish
heart is accessible for continued observation and manipulation at
all stages of development and offers single cell resolution of its
components. Through several genome wide screen in zebrafish, we have
identified a large number of mutations that affect heart formation
and function.
We are currently using the tools of molecular biology, embryology
and genetics to characterize some of these mutations and further our
understanding of the cellular and molecular mechanisms underlying
early cardiac morphogenesis. We are especially interested in studying
early heart induction. Classical embryological studies have revealed
potential roles for both the dorsal organizer and endodermal tissues
in this process. We are thus making use of a number of mutations that
affect either endodermal or myocardial differentiation to approach
this problem. We are also interested in the differentiation of the
endocardial cells and are analyzing a mutation called cloche where
the heart is lacking the endocardial cells. Eight other mutations
affect another aspect of cardiac morphogenesis as they block the fusion
of the primitive myocardial tubes. This block results in the differentiation
of two hearts, one on either side of the midline, a situation commonly
known as cardia bifida. Several of these mutations affect endoderm
development primarily and we have recently directed some of our attention
towards this fascinating yet understudied germ layer.
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Alexander, J. and Stainier, D.Y.R. (1999). A molecular pathway leading to endoderm formation in zebrafish. Current Biology 9 : 1147-1157.
Kupperman, E., An, S., Osborne, N., Waldron, S. and Stainier, D.Y.R. (2000). A sphingosine 1-phosphate receptor regulates cell migration during vertebrate heart development. Nature 406: 192-195.
Kikuchi, Y., Agathon, A., Alexander, J., Thisse, C., Waldron, S., Yelon, D., Thisse, B. and Stainier, D.Y.R. (2001). casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish. Genes & Development 15 : 1493-1505.
Walsh, E.C. and Stainier, D.Y.R. (2001). UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish. Science 293 : 1670-1673.
Horne-Badovinac, S., Rebagliati, M. and Stainier, D.Y.R. (2003). A cellular framework for gut looping morphogenesis in zebrafish. Science 302 , 662-665
information last updated July 2004 |
Biomedical Sciences (BMS) Graduate Program
