|
|
|
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
Click the tab and a window will appear.
List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
| Dr. Selleck's research |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||
The MHE Research Foundation, we comply with the HONcode standard for health trust worthy information: 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
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
The MHE Research Foundation is proud to be working with the EuroBoNeT consortium, a European Commission granted Network of Excellence for
studying the pathology and genetics of bone tumors.
studying the pathology and genetics of bone tumors.
| This website is regularly reviewed by members of the Scientific and Medical Advisory Board of the MHE Research Foundation. All online submission forms use (SSL 3.0, RC4 with 128 bit encryption (High); RSA with 1024 bit exchange) Protocol with Privacy protection. Our goal is to make this website as safe and user friendly as possible. |
| The MHE Research Foundation is a participating member organization of the United States Bone and Joint Decade, (USBJD) & the USBJD Rare Bone Disease Patient Network |
| Email the webmaster: webmaster@mheresearchfoundation.org Materials on this website are protected by copyright Copyright © 2009 The MHE Research Foundation |
| This web page was updated last on 9/19/09, 4:0O pm Eastern time |
| Written consent must be obtained to attach web pages or the files attached to this website. Please email webmaster. |
Disclaimer: While many find the information useful, it is in no way a substitute for professional medical care.
The information provided here is for educational and informational purposes only. This website does not engage in the practice of medicine. In all cases we
recommend that you consult your own physician regarding any course of treatment or medicine.
The information provided here is for educational and informational purposes only. This website does not engage in the practice of medicine. In all cases we
recommend that you consult your own physician regarding any course of treatment or medicine.
The MHE Research Foundation is proud to be an affiliate of the Society For Glycobiology
