Congenital defects occur in up to 10% of all human
pregnancies. A large percentage of these defects involve
the cardiovascular system. 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.
Through an understanding of normal development we
hope to better understand how congenital defects may
occur.
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.
We are now primarily 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. Screening
strategies to identify new candidate genes will be
performed. Studies to determine downstream targets
as well as modifiers of Fgf8 signaling will also be
pursued. In addition we are generating Cre expressing
transgenic mouse lines to perform tissue specific
elimination of Fgf8 to better define its role in various
organ system development. Similar strategies will
also be used to examine and target other candidate
genes to study early patterning of the vertebrate
embryo.
These studies will be performed by pre and post
doctoral candidates who will be trained in state of
the art genetic manipulations to address these questions
in the developing mouse embryo.
See a picture of Dr. Meyer's research
in our Gallery.
