Linked Life Data

16807321

Source:http://linkedlifedata.com/resource/pubmed/id/16807321

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2006-6-29
pubmed:abstractText
Retinal ganglion cell (RGC) axons from each eye execute a series of maneuvers as they converge on the ventral surface of the brain at the optic chiasm for sorting into the optic tracts. Heparan sulfate proteoglycans (HSPGs) are extracellular glycoproteins involved in cell-surface interactions. HSPGs exhibit massive structural diversity, conferred partly by extensive post-translational modification including differential sulfation. Here we examine the roles of HSPG sulfation in RGC axon guidance at the chiasm. We identified different axon navigation phenotypes in two heparan sulfate sulfotransferase (Hst) mutant embryos, Hs2st-/- and Hs6st1-/-, each lacking an enzyme that catalyzes a particular HSPG modification. Hs2st-/- embryos display axon disorganization at the chiasm. Hs6st1-/- embryos exhibit prolific inter-retinal innervation. We show that RGCs express Hs2st and Hs6st1 and that navigation errors made by their axons coincide with regions of high Hs2st and/or Hs6st1 expression at the chiasm. Slit proteins are expressed at particular locations in the retina and around the chiasm and are normally deployed to prevent axons entering inappropriate territories. We show that Hs2st and/or Hs6st1 expression coincides with Slit expression domains at locations where RGC axons make navigation errors in Hs2st-/- and Hs6st1-/- mutants and that Hs6st1-/- RGC axons are less sensitive to Slit2 repulsion than their wild-type counterparts in vitro. We suggest that (1) Hs2st and Hs6st1 are each deployed to generate distinct patterns of heparan sulfation on RGCs and at the optic chiasm and (2) this differential sulfation directs retinal axons through the chiasm, at least in part by modulating the response of the navigating growth cone to Slit proteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6911-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16807321-Alleles, pubmed-meshheading:16807321-Animals, pubmed-meshheading:16807321-Axons, pubmed-meshheading:16807321-Brain, pubmed-meshheading:16807321-Embryo, Mammalian, pubmed-meshheading:16807321-Embryonic Development, pubmed-meshheading:16807321-Eye, pubmed-meshheading:16807321-Heparan Sulfate Proteoglycans, pubmed-meshheading:16807321-Humans, pubmed-meshheading:16807321-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:16807321-Mice, pubmed-meshheading:16807321-Mice, Inbred Strains, pubmed-meshheading:16807321-Mice, Knockout, pubmed-meshheading:16807321-Nerve Tissue Proteins, pubmed-meshheading:16807321-Optic Chiasm, pubmed-meshheading:16807321-Retinal Ganglion Cells, pubmed-meshheading:16807321-Sulfates, pubmed-meshheading:16807321-Sulfotransferases, pubmed-meshheading:16807321-Tissue Distribution, pubmed-meshheading:16807321-Transcription, Genetic
pubmed:year
2006
pubmed:articleTitle
Heparan sulphation patterns generated by specific heparan sulfotransferase enzymes direct distinct aspects of retinal axon guidance at the optic chiasm.
pubmed:affiliation
Genes and Development Group, Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom. t.pratt@ed.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't