Localisation of specific heparan sulfate proteoglycans during the proliferative phase of brain development.
Early brain development is characterised by the proliferation of neural precursor cells. Several families of signalling molecules such as the fibroblast growth factors (FGFs) and Wnts are known to play important roles in this early phase of brain development. Accumulating evidence demonstrates that signalling of these molecules requires the presence of heparan sulfate chains attached to a proteoglycan core protein (HSPG). However, the specific identity of the HSPG components in the developing brain is unknown. To determine which HSPGs might be involved at this early phase, we analysed the expression of the major cell surface HSPG families in the developing brain at a time of most active proliferation. Syndecan-1 and glypican-4 were the most highly expressed in the developing brain during the time of peak proliferation and localise to ventricular regions of the brain, where the precursor cells are proliferating. Syndecan-4, although less abundant, also localises to cells in the ventricular zone. We have also examined HSPG involvement in brain development using cultures of embryonic neural precursor cells. We find that FGF2 stimulation of proliferation is inhibited in the presence of sodium chlorate, an inhibitor of heparan sulfate synthesis, and is rescued by addition of exogenous heparan sulfate. These data support a requirement for heparan sulfate in FGF signalling for proliferation of brain precursor cells. The expression of these specific HSPGs within the proliferative zone of the brain suggests that they may be involved in regulation of early brain development, such as FGF-stimulated proliferation.
Ford-Perriss
Miriam
M
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia. mdfp@unimelb.edu.au
Turner
Kirsty
K
Guimond
Scott
S
Apedaile
Anwyn
A
Haubeck
Hans-Dieter
HD
Turnbull
Jeremy
J
Murphy
Mark
M
D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002704:Chlorates / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D053668:Syndecan-1; D053669:Syndecan-2; D053670:Syndecan-3; D053671:Syndecan-4; D053667:Syndecans
D002704:Chlorates; D053673:Glypicans; C115814:Gpc4 protein, mouse; D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; C508246:Sdc2 protein, mouse; C508302:Sdc3 protein, mouse; C508306:Sdc4 protein, mouse; D053668:Syndecan-1; D053670:Syndecan-3; D053671:Syndecan-4; D053667:Syndecans; C071927:perlecan; D053669:Syndecan-2; D005346:Fibroblast Growth Factors