N-syndecan and HB-GAM (Heparin-Binding Growth-Associated Molecule) associate with early axonal tracts in the rat brain
N-syndecan and HB-GAM (Heparin-Binding Growth-Associated Molecule) associate with early axonal tracts in the rat brain
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DOI：
10.1046/j.1460-9568.1998.00082.x
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发表时间：
1998-02-01
影响因子：
3.4
通讯作者：
Rauvala, H
中科院分区：
文献类型：
--
作者：
Kinnunen, A;Kinnunen, T;Rauvala, H
肝素结合生长相关分子（HB-GAM）/多效生长因子是一种18 kDa的细胞外基质和细胞表面相关蛋白，其显示在体外增强围产期前脑神经元的神经突生长。1994）已被分离为HB-GAM的受体/辅助受体。我们已经调查，是否HB-GAM和N-syndecan可以有类似的作用，在神经突起的生长和轴突的指导在早期轴突束的大脑。在本研究中，发现N-多配体蛋白聚糖与大鼠胚胎第9天已经发育的轴突束在时空上相关，如通过与III类P-微管蛋白的共表达所揭示的，其是最早的神经元标志物之一（Easter等人，1993; Brittis等人，1995年）。后来，N-多配体蛋白聚糖和HB-GAM被检测到的第一个传入神经元投射来自脑桥中缝核。HB-GAM的表达模式在胚胎期（E）13-14在发育中的菱脑中达到峰值。同时，N-多配体蛋白聚糖在发育中的中缝神经元中表达，这些神经元沿着沿着HB-GAM免疫反应通路向间脑生长神经突。当菱脑神经元培养的底物结合HB-GAM浓度下降，E13神经元表现出显着更好的神经突起生长反应比E11，E16或E18神经元。在培养液中加入可溶性肝素或N-多配体聚糖可抑制中缝核神经元突起的生长，而加入硫酸软骨素则无此作用。在一个简单的通路测定，E13中缝神经元选择性地优先附着和生长的神经突起的通路含有HB-GAM相比，区域单独含有层粘连蛋白或纤连蛋白。我们的研究结果表明，HB-GAM可能作为一个发育调节的线索，菱形神经元，拥有N-syndecan在他们的细胞膜上。
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 P-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 Ell, 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.