Peter G. Fuerst, Ph.D.
Assistant Professor
E-Mail: fuerst@vetmed.wsu.edu
Office: 265 Wegner Hall
Phone: (509) 335-8846
Cellular recognition involves a balance of cell adhesion and
repulsion that is critical for many aspects of neuronal circuit
formation. Neurons must extend dendritic arbors of the appropriate size
and shape, have cell bodies that are appropriately spaced from other
cells of the same type, and make functional contacts with their
appropriate synaptic partners. Establishing these parameters requires
that the cells be able to recognize themselves (for dendrite
arborization), their homotypic neighbors (for mosaic spacing and
tiling), and their pre- and postsynaptic targets (for synaptogenesis).
Defects in any of these processes can impact the receptive field
properties of a class of neurons and subsequently alter the function of
the circuits to which they belong. The molecular cues that promote these
recognition and adhesion events, while preventing excessive adhesion to
preserve dendritic arbors and cell body spacing, are only now being
determined.
| Click image for larger view |
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| Retinal ganglion cells labeled with an antibody to
neurofilament |
Transgenic retinal neurons differentially labeled
with red, yellow and blue fluorescent proteins |
Clonal columns in the retina labeled with a
combination of three fluorescent proteins. |
Numerous
adhesion/recognition systems have been explored, such as the neurexin/neuroligins,
the cadherins and protocadherins, and the Immunoglobulin (Ig)
superfamily of Cell Adhesion Molecules (CAMs). In all cases, a major
consideration is the molecular diversity and binding specificities that
are needed for a molecular code that labels neurons for their
integration into circuits.
The Down syndrome cell adhesion molecule, DSCAM, is a member of the Ig-super
family of neural CAMs, and is a candidate protein for such a code.
Vertebrate Dscams are implicated in a number of neurodevelopmental
processes, including preventing adhesion and synaptic pairing.
Vertebrate genomes contain two closely related genes (Dscam and Dscaml1)
and other genes such as the sidekicks (Sdk1 and -2), which encode
structurally similar proteins. The vertebrate genes are not subject to
extensive alternative splicing, implying functional distinctions from
Drosophila Dscam1 that eliminate this requirement.
Our lab is assessing the function of Dscam using transgenic and
mutant mouse models to study how the nervous system develops without
Dscam, or with different levels of Dscam expression. We are examining
the integration of wild type and mutant neurons in chimeric mice to
determine the cell autonomy of DSCAM activity using conditional deletion
and transgenic reporters. In addition we are utilizing an allelic series
of mouse Dscam mutations, by which we hope to separate the various
functions the molecule plays during neurodevelopment.
Biographical Information
Pete received his Bachelor of Arts in Microbiology at The University
of Miami in Oxford, Ohio in 1998. While working on his Ph.D. on the
retrotransposon Ty5 in the Department of Molecular, Cellular and
Developmental Biology at Iowa State University Pete became interested in
developmental neurobiology. Pete pursued a postdoctoral fellowship in
this field at The Jackson Laboratory, in Bar Harbor, Maine and joined
VCAPP in July of 2009.
Selected Publications (click titles for links to publications)
Fuerst, P. G., and Burgess R. W.
Adhesion molecules in establishing retinal circuitry. In
press; Current Opinions in Neurobiology 2009, 19:1-6.
Fuerst, P.G., Koizumi, A., Masland, R.H., and Burgess, R.W. (2008).
Neurite arborization and mosaic spacing in the mouse retina require
DSCAM. Nature 451, 470-474.
Brady, T.L., Fuerst, P.G., Dick, R.A., Schmidt, C., and Voytas, D.F.
(2008). Retrotransposon target site selection by imitation of a cellular
protein. Molecular and Cellular Biology 28, 1230-1239.
Fuerst, P.G., Rauch, S.M., and Burgess, R.W. (2007).
Defects in eye development in transgenic mice overexpressing the heparan
sulfate proteoglycan agrin. Developmental Biology 303, 165-180.
Fuerst, P.G., and Voytas, D.F. (2003). CEN plasmid segregation is
destabilized by tethered determinants of Ty 5 integration specificity: a
role for double-strand breaks in CEN antagonism. Chromosoma 112, 58-65.
Zhu, Y., Dai, J., Fuerst, P.G., and Voytas, D.F. (2003). Controlling
integration specificity of a yeast retrotransposon. Proc. Natl. Acad.
Sci. USA 100, 5891-5895.
