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Zebrafish
Developmental Genetics / Organ Formation
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 that consists of two concentric
epithelial tubes, the outer myocardial tube which forms the muscular component
of the heart, and the inner endocardial tube which 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 cellular and molecular biology, embryology
and genetics to analyze 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 directed some of our attention towards this fascinating
yet understudied germ layer. This work on early endoderm development has
recently progressed to the analysis of another fascinating organ, the
liver. To approach liver formation, we are planning a large-scale mutant
screen using a transgenic line that expresses GFP in the gut and its associated
organs.
Selected Publications:
Alexander, J. and Stainier, D.Y.R. (1999). A molecular pathway leading
to endoderm formation in zebrafish. Current Biology 9:1147-1157.
Reiter, J.F., Alexander, J., Rodaway, A., Yelon, D. Patient, R., Holder,
N. and Stainier, D.Y.R. (1999). Gata5 is required for the development
of the heart and endoderm in zebrafish. Genes & Development 13:2983-2995.
Ho, C., Houart, C., Wilson, S.W., and Stainier, D.Y.R. (1999). A role
for the extraembryonic yolk syncytial layer in patterning the zebrafish
embryo suggested by properties of the Hex gene. Current Biology 9: 1131-1134.
Parker, L.H. and Stainier, D.Y.R. (1999). Cell-autonomous and non-autonomous
requirements for the zebrafish gene cloche in hematopoiesis. Development
126: 2643-2651.
Liao, W., Ho, C.-H., Yan, Y.L., Postlethwait, J. and and Stainier, D.Y.R.
(2000). Hhex and Scl function in parallel to regulate early endothelial
and blood differentiation in zebrafish. Development 127, 4303-4313
Kikuchi, Y., Trinh, L., Reiter, J.F., Alexander, A., Yelon, D. and Stainier,
D.Y.R. (2000). The zebrafish bonnie and clyde gene encodes a Mix family
homeodomain protein that regulates the generation of endodermal precursors.
Genes & Development 14: 1279-1289.
Yelon, D., Ticho, B, Halpern, M., Ruvinsky, I., Ho, R., Silver, L.M. and
Stainier, D.Y.R. (2000). The bHLH transcription factor Hand2 plays parallel
roles in zebrafish heart and pectoral fin development. Development 127:
2573-2582.
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.
Reiter, J.F, Kikuchi, Y. and Stainier, D.Y.R. (2000). Multiple roles for
Gata5 in zebrafish endoderm formation. Development 128: 125-135. Stainier,
D.Y.R. (2001). Zebrafish genetics and vertebrate heart formation. Nature
Review Genetics 2: 39-48.
Contact Information:
Email: didier stainier@biochem.ucsf.edu
Phone: 415/ 502-5679
Address: Box 0448, Room HSE 1508
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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