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Specific modification of heparan sulphate is required for normal cerebral cortical development
a Division of Biomedical Sciences, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh.ORCID iD: 0000-0002-8611-2649
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2003 (English)In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 120, no 12, 1481-1488 p.Article in journal (Refereed) Published
Abstract [en]

Proteoglycans are cell surface and extracellular matrix molecules to which long, unbranched glycosaminoglycan side chains are attached. Heparan sulphate, a type of glycosaminoglycan chain, has been proposed as a co-factor necessary for signalling by a range of growth factors. Here we provide evidence that loss of 2-O-sulphation in heparan sulphate leads to a significant reduction in cell proliferation in the developing cerebral cortex. The gene encoding heparan sulphate 2-sulphotransferase (Hs2st) is expressed in embryonic cortex and histological analysis of mice homozygous for a null mutation in Hs2st indicated a reduction in the thickness of the embryonic cerebral cortex. Using 5′-bromodeoxyuridine (BrdU) incorporation assays we found a reduction of approximately 40% in labelling indices of cortical precursor cells at E12. Comparison of the fates of cortical cells born on E13 and E15 in Hs2st−/− mutant and wildtype littermate embryos revealed no differences in the pattern of cell migration. Our findings suggest a critical role for 2-O-sulphation of heparan sulphate proteoglycan (HSPG) in regulating cell proliferation during development of the cerebral cortex, perhaps through the modulation of cellular responses to growth factor signalling.

Place, publisher, year, edition, pages
Elsevier, 2003. Vol. 120, no 12, 1481-1488 p.
Keyword [en]
Growth factors, Heparan sulphate proteoglycans, Heparan sulphate 2-sulphotransferase, Neural development, Proliferation, Telencephalon, BrdU
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:du-26486DOI: 10.1016/j.mod.2003.08.008OAI: oai:DiVA.org:du-26486DiVA: diva2:1154061
Available from: 2017-11-01 Created: 2017-11-01 Last updated: 2017-11-01Bibliographically approved

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CiteExportLink to record
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Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • chicago-author-date
  • chicago-note-bibliography
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
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  • asciidoc
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