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Heparan sulfate biosynthesis and sulfation:
Exploring function in synapse assembly and vascular development
Abstract 2005 MHE Conference
Scott B. Selleck, Melissa Rusch, Steve Ekker, Catherine Kirkpatrick, and Yi Ren
The Developmental Biology Center, and Depts. of Pediatrics and Genetics,Cell Biology and
Development,The University of Minnesota, Minneapolis, MN 55455
Heparan sulfate is a structurally diverse molecule that is important for both the control of cellular
responses to secreted growth factors, and controlling their distributions in the matrix. Our group
employs a number of model organisms and systems to understand the functions of heparan
sulfate-modified proteoglycans during development.
HSPGs have long been known to be present at the neuromuscular junction in vertebrates, but the
function of this class of molecules has not been explored at this well studied synapse.
We have used mutations affecting the proteins responsible for HS chain initiation (brother of
tout-velu, botv, an ortholog of and Extl), chain polymerization (tout-velu, ttv; sister-of-tout-velu,
sotv, orthologs of vertebrate Ext genes) and sulfation (sulfateless, sfl; ortholog of N-deacetylase
N-sulfotransferase) in the fruitfly Drosophila to assess the role of HS in neuromuscular development
and function.
We find that animals defective for the HS biosynthetic and modifying enzymes show defects in
synaptic transmission. Compensation to presynaptic defects remains however, with increases in
muscle responses and elevated levels of glutamate receptors in the postsynaptic cell.
Our studies of the requirement for HS in vascular development employ the zebrafish Danio rerio.
Using both mutants affecting Ext2 and Extl3 (boxer and dackel, respectively), as well as morpholinos
directed against the mRNAs from these genes, we have found that HS synthesis is required for
normal angiogenesis in zebrafish embryos.
We have also established methods for identifying small molecule inhibitors of HS synthesis and
modification using human tissue culture cells. A small molecules derived from this screen affects HS
biosynthesis in zebrafish embryos and likewise disrupts normal vascular development.
Exploring function in synapse assembly and vascular development
Abstract 2005 MHE Conference
Scott B. Selleck, Melissa Rusch, Steve Ekker, Catherine Kirkpatrick, and Yi Ren
The Developmental Biology Center, and Depts. of Pediatrics and Genetics,Cell Biology and
Development,The University of Minnesota, Minneapolis, MN 55455
Heparan sulfate is a structurally diverse molecule that is important for both the control of cellular
responses to secreted growth factors, and controlling their distributions in the matrix. Our group
employs a number of model organisms and systems to understand the functions of heparan
sulfate-modified proteoglycans during development.
HSPGs have long been known to be present at the neuromuscular junction in vertebrates, but the
function of this class of molecules has not been explored at this well studied synapse.
We have used mutations affecting the proteins responsible for HS chain initiation (brother of
tout-velu, botv, an ortholog of and Extl), chain polymerization (tout-velu, ttv; sister-of-tout-velu,
sotv, orthologs of vertebrate Ext genes) and sulfation (sulfateless, sfl; ortholog of N-deacetylase
N-sulfotransferase) in the fruitfly Drosophila to assess the role of HS in neuromuscular development
and function.
We find that animals defective for the HS biosynthetic and modifying enzymes show defects in
synaptic transmission. Compensation to presynaptic defects remains however, with increases in
muscle responses and elevated levels of glutamate receptors in the postsynaptic cell.
Our studies of the requirement for HS in vascular development employ the zebrafish Danio rerio.
Using both mutants affecting Ext2 and Extl3 (boxer and dackel, respectively), as well as morpholinos
directed against the mRNAs from these genes, we have found that HS synthesis is required for
normal angiogenesis in zebrafish embryos.
We have also established methods for identifying small molecule inhibitors of HS synthesis and
modification using human tissue culture cells. A small molecules derived from this screen affects HS
biosynthesis in zebrafish embryos and likewise disrupts normal vascular development.
Research authored by Dr. Selleck
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
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Dr. Selleck's research
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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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