Research Interests:
My laboratory is interested in the myriad effects of growth factor
signaling in nervous system development and synaptic plasticity.
Much of our work is based in the fruitfly Drosophila melanogaster,
an organism with an unparalleled set of genetic and molecular tools.
However, we also have projects in three vertebrate systems, zebrafish,
mouse and humans. It is our philosophy that studies in Drosophila
serve as the basic molecular and cellular underpinnings that can
be then extended into more complex systems.
We began this work with a search for genes affecting the spatial
control of cell division during visual system assembly in Drosophila.
This screen identified a class of cell surface molecules that regulate
a number of growth factor signaling pathways during development,
including the Wnt, BMP and Hh families of secreted proteins(Selleck,
2000; Tsuda et al., 1999). Glypicans are GPI-linked and heparan
sulfate modified proteins, represented by two genes in Drosophila
and 6 in most vertebrates, including humans. These molecules bind
growth factors and modulate their signaling by both affecting their
distribution in tissues, as well as modulating cellular responses,
presumably by serving as growth factor co-receptors. Both Drosophila
genes control neuronal differentiation and cell division patterning
in the developing visual system(Nakato et al., 2002; Selleck et
al., 1992).
More recently we have been working on the molecular determinants
of synapse development and remodeling. A recent publication from
our group established that signaling by the TGF- /BMP family of
growth factors is critical for synapse assembly and function in
Drosophila(Rawson et al., 2003). This analysis involved both morphological
and physiological measures of synapse development at the neuromuscular
junction.
At present we have a number of neurodevelopment projects in the
laboratory. We are examining the role of heparan sulfate proteoglycans,
and glypicans in particular, in controlling axon guidance during
embryonic CNS and adult visual system assembly in Drosophila. Another
effort examines how growth factors and proteoglycans influence assembly
of the neuromuscular synapse in Drosophila. Our long term objective
is to extend these studies to the mouse and in collaboration with
Dr. Mike O'Connor we have established a system for examining long
term potentiation in the hippocampus. This physiological tool will
be combined with genetic methods to examine the role of molecules
affecting growth factor signaling in synapse plasticity.
Finally, we have recently started a human genetics project to identify
the molecular mechanisms contributing to autism. A number of twin
studies have demonstrated a substantial genetic basis for autism
spectrum disorders. Based on these findings we are characterizing
the chromosomal abnormalities associated with autism in families
identified through the University of Minnesota clinics. Ultimately,
we wish to identify those genes that predispose toward autism spectrum
disorders as a means of understanding the molecular and cellular
basis of this disease that is affecting an increasing number of
families in the U.S.
Selected Publications:
Sun M, Thomas MJ, Herder R, Bofenkamp ML, Selleck SB, O'Connor MB. Presynaptic contributions of chordin to hippocampal plasticity and spatial learning. J Neurosci. 2007 Jul 18;27(29):7740-50.
Kirkpatrick CA, Selleck SB. Heparan sulfate proteoglycans at a glance. J Cell Sci. 2007 Jun 1;120(Pt 11):1829-32.
Knox S, Ge H, Dimitroff BD, Ren Y, Howe KA, Arsham AM, Easterday MC, Neufeld TP, O'Connor MB, Selleck SB. Mechanisms of TSC-mediated control of synapse assembly and axon guidance. PLoS ONE. 2007 Apr 18;2(4):e375.
Balciuniene J, Feng N, Iyadurai K, Hirsch B, Charnas L, Bill BR, Easterday MC, Staaf J, Oseth L, Czapansky-Beilman D, Avramopoulos D, Thomas GH, Borg A, Valle D, Schimmenti LA, Selleck SB. Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities. Am J Hum Genet. 2007 May;80(5):938-47.
Kirkpatrick CA, Knox SM, Staatz WD, Fox B, Lercher DM, Selleck SB. The function of a Drosophila glypican does not depend entirely on heparan sulfate modification.
Dev Biol. 2006 Dec 15;300(2):570-82.
Selleck SB. Signaling from across the way: transactivation of VEGF receptors by HSPGs. Mol Cell. 2006 May 19;22(4):431-2.
Selleck SB. Shedding light on the distinct functions of proteoglycans. Sci STKE. 2006 Apr 4;2006(329):pe17.
Current Graduate Students:
Bridget Campion (Neuroscience, University of Minnesota).
Katie Howe (Neuroscience, University of Minnesota).
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