Heparan sulphate and HB-GAM (heparin-binding growth-associated molecule) in the development of the thalamocortical pathway of rat brain
Heparan sulphate and HB-GAM (heparin-binding growth-associated molecule) in the development of the thalamocortical pathway of rat brain
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DOI：
10.1046/j.1460-9568.1999.00457.x
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发表时间：
1999-02-01
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;Niemi, M;Rauvala, H
细胞外基质（ECM）分子，如层粘连蛋白，腱生蛋白，硫酸软骨素蛋白聚糖和硫酸乙酰肝素蛋白聚糖已被认为具有“路标”和指导作用，在皮层发育的轴突投射的形成。我们在这里表明，神经突生长促进蛋白肝素结合生长相关分子（HB-GAM）和N-多配体聚糖，一种跨膜硫酸乙酰肝素蛋白聚糖先前分离的受体为HB-GAM的表达，是时空相关的发展丘脑皮质通路在大鼠大脑。使用原位杂交，丘脑神经元表达N-多配体蛋白聚糖的mRNA，并在体外，丘脑神经元生长更多的神经突起上HB-GAM比层粘连蛋白。HB-GAM诱导的丘脑神经元突起生长被肝素酶、肝素、可溶性N-多配体聚糖和培养基中过量的可溶性HB-GAM抑制。在通路分析中，丘脑神经元选择性地偏好在含有HB-GAM的基质上附着和生长神经突，而不是在单独含有纤连蛋白或层粘连蛋白的基质上，这表明HB-GAM可以调节其他ECM蛋白的作用。在未固定的脑切片制备，丘脑神经元反复表现出典型的神经突起生长和附着模式类似的HB-GAM的表达模式。在脑片上，神经突起生长被肝素酶、肝素和可溶性HB-GAM显著抑制，从而显示了神经突起在基质结合HB-GAM上生长的特征。我们的研究结果表明，HB-GAM是重要的丘脑神经元的轴突生长，它可能作为一个ECM结合的丘脑神经元，具有HB-GAM结合硫酸乙酰肝素在其细胞膜上的指导线索。
Extracellular matrix (ECM) molecules, such as laminin, tenascin, chondroitin sulphate proteoglycans and heparan sulphate proteoglycans have been suggested to have 'signpost' and directing roles in the formation of axonal projections in cortical development. We show here that the expression of the neurite outgrowth-promoting protein heparin-binding growth-associated molecule (HB-GAM) and N-syndecan, a transmembrane heparan sulphate proteoglycan previously isolated as a receptor for HB-GAM, is spatiotemporally associated with the developing thalamocortical pathway in the rat brain. Using in situ hybridization, thalamic neurons were shown to express mRNA for N-syndecan, and in vitro, thalamic neurons grew more neurites on HB-GAM than on laminin. The HB-GAM-induced neurite outgrowth in thalamic neurons was inhibited by heparitinase, heparin, soluble N-syndecan and by an excess of soluble HB-GAM in the culture medium. In a pathway assay, thalamic neurons selectively preferred attaching and growing neurites on matrices containing HB-GAM than on those containing fibronectin or laminin alone, suggesting that HB-GAM may modulate the effect of other ECM proteins. On an unfixed brain slice preparation, thalamic neurons repeatedly showed a typical neurite outgrowth and attachment pattern resembling the expression pattern of HB-GAM. On the brain slices, the neurite outgrowth was significantly inhibited by heparitinase, heparin and soluble HB-GAM, thus displaying features of neurite outgrowth on matrix-bound HB-GAM. Our results suggest that HB-GAM is important for the neurite outgrowth of thalamic neurons and it may function as an ECM-bound guidance cue for thalamic neurons that possess HB-GAM-binding heparan sulphates on their cell membrane.