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Specific modification of heparan sulphate is required for normal cerebral cortical development.

TitleSpecific modification of heparan sulphate is required for normal cerebral cortical development.
Publication TypeJournal Article
Year of Publication2003
AuthorsMcLaughlin D, Karlsson F, Tian N, Pratt T, Bullock SL, Wilson V, Price DJ, Mason JO
JournalMech Dev
Volume120
Issue12
Pagination1481-8
Date Published2003 Dec
ISSN0925-4773
KeywordsAnimals, Bromodeoxyuridine, Cell Division, Cell Movement, Cerebral Cortex, Gene Deletion, Heparan Sulfate Proteoglycans, Heparitin Sulfate, Mice, Mice, Knockout, Sulfates, Sulfotransferases
Abstract

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.

Alternate JournalMech. Dev.
PubMed ID14654220