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

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.

journal_name

Mech Dev

authors

McLaughlin D,Karlsson F,Tian N,Pratt T,Bullock SL,Wilson VA,Price DJ,Mason JO

doi

10.1016/j.mod.2003.08.008

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

1481-8

issue

12

eissn

0925-4773

issn

1872-6356

pii

S0925477303002168

journal_volume

120

pub_type

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