N‐Syndecan and HB‐GAM (Heparin‐Binding Growth‐Associated Molecule) associate with early axonal tracts in the rat brain

Abstract

Heparin-Binding Growth-Associated Molecule (HB-GAM)/pleiotrophin is an 18 kDa extracellular matrix- and cell-surface-associated protein shown to enhance neurite outgrowth of perinatal forebrain neurones in vitro. The heparan sulphate proteoglycan N-syndecan (Raulo et al., 1994) has been isolated as a receptor/coreceptor for the HB-GAM. We have investigated, whether HB-GAM and N-syndecan could have a similar role in neurite outgrowth and axon guidance in early axonal tracts of brain. In the present study N-syndecan was found to be spatiotemporally associated with the developing axonal tracts already on embryonic day 9 in rat, as revealed by coexpression with class III beta-tubulin, which is one of the earliest neuronal markers (Easter et al., 1993; Brittis et al., 1995). Later, N-syndecan and HB-GAM were detected in the first afferent serotonergic projections arising from the pontine raphe nuclei. The expression pattern of HB-GAM peaked in the developing rhombencephalon at embryonic stage (E) 13-14. At the same time, N-syndecan was expressed in the developing raphe neurones growing neurites towards the diencephalon along HB-GAM immunoreactive pathways. When rhombencephalic neurones were cultured on decreasing concentrations of substrate-bound HB-GAM, E13 neurones showed a significantly better neurite outgrowth response than E11, E16 or E18 neurones. The neurite outgrowth of raphe neurones in vitro was inhibited by adding soluble heparin or N-syndecan into the culture medium, whereas addition of chondroitin sulphate had no effect. In a simple pathway assay, E13 raphe neurones selectively preferred attaching and growing neurites on pathways containing HB-GAM as compared with regions containing either laminin or fibronectin alone. Our results suggest that HB-GAM may function as a developmentally regulated cue for rhombencephalic neurones that possess N-syndecan on their cell membrane.

Differential expression of syndecan isoforms during mouse incisor amelogenesis

“…Both syndecan-2 and -3 are expressed in neurons of developing forebrain of rat, but have different functions (20,21). In neurons, syndecan-2 is located in synaptic junctions and is considered to contribute to tight cell-cell adhesion at these sites (20), whereas syndecan-3 is seen in growth cones and axons, and thought to be concerned with neural outgrowth (21).…”

Gene Expression Changes in the Course of Neural Progenitor Cell Differentiation

“…In the context of our report, some are of special interest (Li et al, 1990; for review, see Deuel et al, 2002;Muramatsu 2002). It stimulates the migration of embryonic neurons, is present in radial glial processes, and localizes along neuronal migration routes (Matsumoto et al, 1994;Rauvala et al, 1994;Wewetzer et al, 1995;Nolo et al, 1996;Silos-Santiago et al, 1996;Kinnunen et al, 1998Kinnunen et al, , 1999Maeda and Noda, 1998). The migratory effect is mediated through the binding of Pleiotrophin to the transmembrane protein-tyrosine phosphatase PTP on migrating neurons (Maeda and Noda, 1998).…”

“…Syndecan-3 is a transmembrane proteoglycan that binds to extracellular ligands and regulates signaling and cytoskeletal organization during developmental processes. It is localized to axons in the developing brain and to oligodendrocyte progenitors (Kinnunen et al, 1998;Hsueh and Sheng, 1999;Winkler et al, 2002) (for review, see Rapraeger, 2001).…”

Characterization of Heparin Affin Regulatory Peptide Signaling in Human Endothelial Cells

“…Additionally, an analysis of tyrosine-phosphorylated proteins following HARP stimulation showed induction of Shc and Erk1/2 phosphorylation (15). Nevertheless, the signals from specific receptors to PI3K or MAPK are still not well documented, although it has been hypothesized that Src is involved in the process (18,19).…”