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Return to: College of Biological Sciences: Medical School: U of M Home |
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Areas of Research Strength: Regulation of growth factor signaling Proteoglycan modulation of morphogen function Nervous system assembly and synapse development back to top |
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Research Techniques: Molecular Genetics Confocal and conventional light microscopy Electrophysiology of carbohydrate structures back to top |
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Research Interests: The Selleck laboratory is interested in how growth factor signaling shapes the development and function of the nervous system. These studies range from exploring the molecular determinants of signaling molecule gradients to the genetics of behavioral disorders in children. Their principal model system is the fruitfly, Drosophila melanogaster, which provides a wide array of powerful genetic, molecular and cellular methods to understand gene function. In addition to providing a system to identify novel genes affecting nervous system assembly, they employ Drosophila to understand the function of candidate disease genes identified from human genetic studies. A principal effort in the lab is to understand how heparan sulfate proteoglycans, an abundant class of cell surface and matrix molecules, affect nervous system patterning and assembly. Initial studies demonstrated that a GPI-linked heparan sulfate proteoglycan encoded by division abnormally delayed (dally) was responsible for controlling cell cycle progression and growth factor signaling in the visual system (Nakato et al. 1995; Jackson et al. 1997). More recent work has established that glypicans pattern the nervous system by both controlling cell responses to Wnt and BMP-related ligands as well as dictating the levels of these signaling molecules in the matrix (Tsuda et al. 1999; Fujise et al. 2001; Kirkpatrick et al. 2004). The lab has also discovered that two distinct Drosophila HSPGs, a glypican and a syndecan, are expressed at high levels on axons and play distinct roles in axon guidance in the Drosophila visual system (Rawson et al. 2005). The neuromuscular junction in Drosophila has provided a system to understand the molecular control of synapse development and plasticity. The Selleck lab was one of several groups to demonstrate that BMP signaling is essential for normal NMJ assembly and physiological function (Rawson et al. 2003). Current work examines the requirements for HSPGs in synapse assembly and function. The lab’s recent human genetic studies were initiated by the identification of a large kindred with autism and developmental delay through the University of Minnesota clinics. They have identified a region of chromosome 10 susceptible to rearrangements that can contribute to abnormal behavioral development in children. Their studies now include detailed genomic and genetic mapping of chromosome 10 contributions to autism and the analysis of candidate genes using Drosophila. Other studies in the lab examine the function of HSPGs in vascular and blood development using the zebrafish, Danio rerio, in collaboration with Dr. Steve Ekker (Chen et al. 2005). back to top |
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Selected Publications: Kirkpatrick, C., and Selleck, S.B. (2007). Heparan sulfate proteoglycans at a glance. J Cell Sci. 2007 Jun 1;120(Pt 11):1829-32 Sun, M., Thomas, M.J., Herder, R., Selleck, S.B., and O’Connor, M.B. (2007). Presynapatic contributions of Chordin to hippocampal plasticity and spatial learning. J Neurosci. 2007 Jul 18;27(29):7740-50 Dasgupta, U., Dixit, B.L., Rusch, M., Selleck, S.B., The, I. (2007). Functional conservation of the human EXT1 tumor suppressor gene and its Drosophila homolog tout velu. Dev. Genes & Evo. (in press). Knox,S. M.* , Ge,H.*, Dimitroff, B.D., Ren, Y., Howe, K., Easterday, M., Arsham,A. M., Neufeld,T. P., & O’Connor, M., Selleck, S. B. (2007) Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance PLoS ONE Apr 18;2:e375. * contributed equally. Balciuniene*, J. Feng*, N-P., Iyadurai, K. , Hirsch, B., Charnas, L., Bill, B., Staaf, J., Oseth L., Roberts, W., Avramopoulos, D., Borg Å, Valle, D., Schimmenti, L., Selleck,, S.B. (2007). Recurrent 10q22-23 deletions: A Genomic disorder on 10q associated with cognitive and behavioral abnormalities. AJHG 80(5):938-47. * contributed equally Kirkpatrick C.A., Knox S.M., Staatz W.D., Fox B., Lercher D.M., Selleck, S.B. (2006) The function of a Drosophila glypican does not depend entirely on heparan sulfate modification. Dev Biol. 300: 570-582 Pan, C. Nelson, M.S., Reyes, M., Koodie, L., Brazil, J.L., Stephenson, E.J., Zhao, R.C., Peters, C., Selleck, S.B., Stringer, S. and Gupta, P. (2005) Functional abnormalities in heparan sulfate mucopolysaccharidosis-1 are associated with defective biological activity of FGF-2 on human multipotent progenitor cells. Blood 15;106(6): 1956-64 Chen, E., Stringer, S.E., Rusch, M.A., Selleck, S.B.* and Ekker, S.E.* (2005) A unique role for 6-O sulfation modification in zebrafish vascular development. Dev Biol 284(2): 364-76. *joint corresponding authors. Rawson, J. M., Johnson, K. B.,Ge, X., Van Vactor, D., and Selleck, S.B. (2005) The Heparan Sulfate Proteoglycans Dally-like and Syndecan Have Distinct but Overlapping Functions in Axon Guidance and Visual System Assembly in Drosophila. Curr Biol 15(9): 833-838. Lee, J-S., von der Hardt,S., Rusch, M.*, Stringer,S.*, Stickney,H., Talbot, W., Geisler, R., Nusslein-Volhardt, C., Selleck, S.B., Chien, C-B., and Roehl, H. Axon sorting in the optic tract requires HSPG synthesis by EXT2/dackel and EXTL3/boxer. Neuron 44(6):947-960. Ledin, J., Staatz, W., Gotte, M., Selleck, S.B., Kjellen, L., and Spillmann, D. (2004) Heparan sulfate structure in mice with genetically modified heparan sulfate production. JBC 279(41):42732-42741. Kirkpatrick, C., Dimitroff, B., Rawson, J. and Selleck, S.B. (2004) dally-like, a Drosophila glypican, controls the distribution and signaling of the Wingless morphogen. Dev. Cell. 7(4): 513-523. Bornemann, D.J., Duncan, J.E., Staatz, W., Selleck, S.B. and Warrior, R. (2004) Abrogation of heparan sulfate synthesis in Drosophila disrupts Wingless, Hedgehog and Decapentaplegic signaling pathways. Development 131(9):1927-1938. Rawson, J., Lee, M. and Selleck, S.B. (2003) Drosophila neuromuscular synapse assembly and function require the TGF-ß type I receptor Saxophone and the transcription factor Mad. J. Neurobio 55(2):134-150. Nakato, H., Fox, B., and Selleck, S.B. 2002. dally, a Drosophila member of the glypican family of integral membrane proteoglycans, affects cell cycle progression and morphogenesis via a Cyclin A-mediated process. J. Cell Sci. 115: 123-130. To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed search menu should say PubMed type Selleck SB in the avaliable line back to top |
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| dally-like mutant photoreceptor projections to the Drosophila brain, showing one axon bundle with an ectopic process (arrow). |
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| dally-like mutants show ectopic assembly of mechanosensory bristles (arrows, lower panel) on the margin of the wing blade, a consequence of elevated levels of Wingless signaling. |
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| Fluorescence in situ hybridization mapping of a deletion affecting behavioral development in children (nl=normal chromosome, del=deleted chromosome). |
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