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Eric
S. Weinberg
Professor,
Dept of Biology
Developmental,
Stem Cell and Regenerative Biology Program
Address
Lynch
Laboratories (204E, office; 223, lab)
Office tel.: 215-898-4198
Lab tel.: 215 898-2640
Fax: 215 898-8780
E-mail: eweinber@sas.upenn.edu
Education
University of Rochester, B.A. (Chemistry),1963
Rockefeller University, Ph.D. (Developmental Biology), 1969
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Research
Interests
- Our lab is involved in a set of projects
on the control of pattern formation in the zebrafish embryo,
focusing mainly on the signaling pathways involved dorsoventral
and anteroposterior patterning.
Key
words: zebrafish, neural development,
brain, ear, sensory ganglia, organizer, beta-catenin.
Description
of Research
Our lab is involved in a set of projects on
the control of pattern formation in the zebrafish embryo,
focusing mainly on the signaling pathways involved dorsoventral
and anteroposterior patterning.
- Roles of the two zebrafish β-catenins
in formation of the embryonic organizer
One of the most fundamental issues in embryonic development
is how the anterior-posterior and dorsal-ventral axes are
determined. This patterning is controlled in part by a dorsal
tissue termed 'the organizer' whose formation is dependent
on signaling through the Wnt/?-catenin pathway. The zebrafish
has two β-catenin genes, and we have shown that organizer
formation is completely dependent on one of these two genes,
β-catenin-2. We have characterized a maternal effect
mutation (ichabod) that has a chromosomal rearrangement
near the β-catenin-2 gene, specifically resulting
in a decrease in maternal transcripts from this gene and
a consequent failure of embryos to form the dorsal organizing
center. Morpholino oligonucleotide knock-down experiments
confirm a requirement for ?-catenin-2 and not β-catenin-1.
The two ?-catenin proteins are very similar in sequence
(93% identity) and both transcripts are expressed ubiquitously.
Using an antibody specific for ?-catenin-1, we have found
that this protein is expressed in prospective dorsal organizer
cells but is less frequently located in nuclei than is β-catenin-2.
The two proteins differ most in the 100 C-terminal amino
acids and it is possible that this domain confers preferential
interactions with particular binding partners. The control
of such processes has importance beyond the study of organizer
formation, as the partition of β-catenin between the
nucleus and cadherin located in the cell membrane is a key
factor in whether the protein acts as an oncogen.
- Interaction between Nodal and FGF
signaling pathways in induction of dorsal mesoderm
Using wild-type and ichabod mutant embryos, we have worked
out the pathway of genes activated by beta-catenin-2 in
the organizing center. FGF signaling is essential for organizer
formation and this signaling is activated by beta-catenin-2
acting through Nodal signals. FGFs in the organizer are
essential for dorsal chordin expression and are also essential
for control of stability of transcripts for a key organizer
transcription factor, Bozozok. Using transplantation experiments,
we have now shown that FGF signaling is required for Nodal
induction of chordin, noggin1, goosecoid, and no tail (Brachyury),
but not for induction of FGF genes. FGFs might thus be intermediate
signaling molecules (relays) under some conditions. We are
currently pursuing experiments to distinguish between relays
and a requirement for autocrine FGF signaling in responding
cells.
Selected
Publications
Gore, A., Maegawa, S., Gilligan, P., Weinberg,
E.S., and Sampath, K. (2005). The zebrafish dorsal axis is
specified by the 4-cell stage. Nature 438: 1030-1035.
Bellipanni, G., Varga, M., Maegawa, S., Imai,
Y., Kelly, C., Pomrehn, A., Chu, F., Talbot, W.S., and Weinberg,
E.S. (2006). Essential and opposing roles of zebrafish β-catenins
in formation of dorsal axis structures and development of
neurectoderm. Development 133: 1299-1309.
Maegawa, S., Varga, M., and Weinberg, E.S. (2006).
FGF signaling is required for β-catenin-mediated induction
of the zebrafish organizer. Development 133: 3265-3276.
Varga, M., Maegawa, S., Bellipanni, G., and
Weinberg, E.S. (2007). Chordin expression, mediated by Nodal
and FGF signaling is restricted by redundant function of two
β-catenins in the zebrafish embryo. Mech. Dev. 124:
775-791.
Tang, X., Maegawa, S., Weinberg, E.S., and Dmochowski,
I.J. (2007). Regulating gene expression in zebrafish embryos
using light-activated antisense peptide nucleic acids. J.
Am. Chem. Soc. 129: 11000-11001.
Search PubMed for articles
Lab
Rotation
Projects
Dr. Weinberg will be on sabbatical for part of this academic
year and will not be taking on rotation students.
- Lab
personnel:
- Gianfranco Bellipanni, Research Fellow
Joshua Bradner, Research Specialist
Jared Rudick, Research Specialist
last updated 9/2008
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