| First Author | McLaughlin D | Year | 2003 |
| Journal | Mech Dev | Volume | 120 |
| Issue | 12 | Pages | 1481-8 |
| PubMed ID | 14654220 | Mgi Jnum | J:123454 |
| Mgi Id | MGI:3718318 | Doi | 10.1016/j.mod.2003.08.008 |
| Citation | McLaughlin D, et al. (2003) Specific modification of heparan sulphate is required for normal cerebral cortical development. Mech Dev 120(12):1481-8 |
| abstractText | 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. |
