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Erik
N. Meyers, MD
(Neonatology,
UC San Francisco)
Assistant Professor,
Department of Pediatrics,
Cell Biology/Developmental Biology
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Congenital
defects occur in up to 10% of all human pregnancies. A
large percentage of these defects involve the neural and
cardiovascular systems. In a broad sense my lab is interested
in defining the molecular signals guiding the early patterning
of the vertebrate embryo with emphasis on organogenesis
and cardiovascular development. By generating mouse genetic
models of congenital defects, we hope to better understand
how these defects may occur in humans.
The early patterning of the vertebrate
embryo results from a complex milieu of signals to guide
growth, differentiation and migration of cells to their
proper position and specification. Utilizing modern genetic
techniques, we are attempting to dissect these signals
through loss and gain of function experiments. As an example,
utilizing the Cre/LoxP and Flp/Frt recombination systems,
we have targeted the murine Fgf8 gene locus to perform
loss of function studies. Using this approach we have
determined that Fgf8 is required not only during gastrulation,
limb outgrowth, and CNS development but is also required
as a left-right axis determinant as well. From its earliest
stages, the cardiovascular system is patterned in a left-right
asymmetric manner. Loss of Fgf8 function can result in
a phenotype similar to the human "asplenia"
syndrome where left-sided structures are mispecified as
right. This results in characteristic complex cardiovascular
defects. Using a variety of Cre transgenic mouse lines,
we are now dissecting the role of Fgf8 in various aspects
of cardiovascular patterning. Studies to determine downstream
targets as well as modifiers of Fgf8 signaling are also
being pursued.
We are also interested in identifying
other genes that establish and pattern the cardiovascular
system, with particular attention paid to those signals
involved in left-right axis determination. In addition
we are using or generating transgenic mouse lines to perform
tissue specific gain and loss of function studies to test
candidate genes. Experiments using organ culture and chick
"in Ovo" experimentation are also used to test
candidate genes involved in cardiovascular patterning.
In addition to cardiovascular patterning,
we are studying neural tube closure and the role Fgf signaling
has in this process. Infants born with neural tube defects
suffer from multiple medical complications including paralysis
or even death. While much progress has been made in management,
the genetic mechanisms by which these defects occur remain
largely unknown. Recent evidence in gain and loss of function
studies in mouse embryos suggests a role for Fgf signaling
in Neural tube closure. Using Cre/LoxP technology, we
are generating transgenic mouse lines to study gain and
loss of Fgf signaling during neural tube closure. |
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E-mail
e.meyers@cellbio.duke.edu
4025 GSRBII Bldg., Box 3709
Duke University Medical Center
Durham, NC 27710
Telephone
919-681-8408
Fax
919-681-6065
Lab Website
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Selected
Publications
Sun, X. Lewandoski, M., Meyers, E.N., Liu, Y.-H, Maxson,
R.E., Jr. and Martin, G.R. Conditional inactivation of
Fgf4 reveals complexity of signaling during limb bud development.
Nature Genet. 25, 83-86. 2000
Meyers, E.N. and Martin, G.R. Differences between mouse
and chick Left-Right asymmetry pathways: roles of FGF8
and SHH. Science Jul 16; 285(5426):403-6, 1999.
Meyers, E.N., Lewandoski, M., and Martin, G. R. An Fgf8
mutant allelic series generated by Cre-and Flp- mediated
recombination. Nature Genet. 18:2, p 136-142, 1998.
Sun, X., Meyers, E.N., Lewandoski, M., and Martin, G.R.
Targeted disruption of Fgf8 causes failure of cell migration
in the gastrulating mouse embryo. Genes and Dev. July
15; 13(14): 1834-46, 1999.
Lewandoski, M., Meyers, E.N. & Martin G.R. Analysis
of Fgf8 Gene Function in Vertebrate Development. Cold
Spring Harbor Symp. Quant. Bio. Vol. LXII p 159-167 1998. |
Current
Projects
Identifying modulators and/or downstream targets of the
Fgf8 signaling pathway.
Cardiovascular specific elimination of Fgf8 using Cre/LoxP
technology.
Screens for candidate genes involved in cardiovascular
and other organ system patterning.
Analyses of the role of Fgf signaling in neural tube closure.
Analysis of candidate genes involved in cardiovascular
patterning.
The Laboratory is in its initial stages and looking to
expand to address the above projects. |
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