ROLE OF ASTROGLIAL EXTRACELLULAR-MATRIX IN THE FORMATION OF RAT OLFACTORY-BULB GLOMERULI
ROLE OF ASTROGLIAL EXTRACELLULAR-MATRIX IN THE FORMATION OF RAT OLFACTORY-BULB GLOMERULI
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DOI：
10.1006/exnr.1993.1143
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发表时间：
1993-09-01
影响因子：
5.3
通讯作者：
SILVER, J
中科院分区：
文献类型：
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作者：
GONZALEZ, MD;MALEMUD, CJ;SILVER, J
我们描述了嗅球（OB）肾小球的发展，重点是所谓的星形胶质细胞相关的边界分子的作用。作为肾小球形成的潜在指导因子。肾小球是OB内的不寻常结构，由无法深入大脑的非常紧密的传入纤维束形成。使用嗅觉标记蛋白抗体，我们发现，嗅觉轴突的阶段E17-E18大鼠胚胎组织成长链的最外边缘的灯泡。到E20-E21，轴突聚集并形成小球，到PD 1，它们聚集成不同的肾小球。之前和期间的嗅觉传入到肾小球的转化，有一个增强的表达的cytoprotein/tenascin（CT）和硫酸软骨素蛋白多糖（CSPG）与Vim/GFAP阳性星形胶质细胞的过程中的肾小球的基础。在发育的后期（PD 3-PD 9），肾小球基底下和内部的GFAP阳性星形胶质细胞突起显示出增强的GFAP染色，同时保持CT和CS-PG的表达。一些星形胶质细胞突起已经延伸，另一些甚至进一步向外周进入嗅神经层（ONL）以包裹并完全浸润肾小球。到PD 9时，肾小球内外CS-PG和CT水平升高。然而，到PD 15时，两种分子在肾小球内都减少了，但仍高度集中在肾小球周围形成环。因此，在后期阶段，轴突/神经胶质细胞的相互作用，导致星形胶质细胞的重排和基质的改变，肾小球发生。E20期鳞茎蛋白的Western印迹显示存在三种蛋白聚糖核心蛋白，每种蛋白聚糖核心蛋白含有软骨素-6-硫酸酯部分。此外，一种类型的硫酸角质素（KS）糖胺聚糖存在于与6-硫酸软骨素无关的核心蛋白中。我们的数据表明，星形胶质细胞相关的ECM分子CT和CSPG，也许KS-PG，存在于早期发展的OB的核心，可以形成一个分子“墙”，有助于限制向内生长的嗅觉轴突内的ONL的外边缘的星形胶质细胞的领土。我们认为，星形胶质细胞不精确地调节特定形状的肾小球，而是发挥了根本性的作用，指导总的位置，在那里形成的突触肾小球将发生。
We describe the development of the olfactory bulb (OB) glomeruli, focusing on the role of purported astroglial-associated boundary molecules. as potential guidance factors in glomeruli formation. Glomeruli are unusual structures within the OB formed by extremely tight bundles of afferent fibers that fail to grow deeply into the brain. Using olfactory marker protein antibodies, we found that olfactory axons of stage E17-E18 rat embryos were organized into long strands at the outermost edge of the bulb. By E20-E21 the axons clustered and formed small spheres and by PD1 they gathered into distinct glomeruli. Prior to and during the transformation of olfactory afferents into glomeruli, there was an enhanced expression of cytotactin/tenascin (CT) and chondroitin sulfate-containing proteoglycan (CSPG) associated with VIM/GFAP-positive astroglial cell processes at the base of the glomeruli. During later stages of development (PD3-PD9), the GFAP-positive astroglial processes beneath and within the base of the glomeruli showed intensified GFAP staining while maintaining expression of CT and CS-PG. Some astroglial processes had extended and others went even further peripherally into the olfactory nerve layer (ONL) to encapsulate and fully infiltrate the glomeruli. By PD9, CS-PG and CT levels increased inside and outside the glomeruli. However, by PD15 both molecules had decreased inside the glomeruli but remained highly concentrated around the glomeruli to form rings. Thus, at later stages, axon/glia interactions which result in astroglial rearrangement and matrix alterations in relation to the glomeruli occur. Western blots of stage E20 bulb proteins revealed the presence of three proteoglycan core proteins each containing chondroitin-6-sulfate moieties. In addition, a type of keratan sulfate (KS) glycosaminoglycan was present in a core protein not associated with chondroitin-6-sulfate. Our data suggest that astroglial-associated ECM molecules CT and CSPG, and perhaps KS-PG, present in the core of the early developing OB, could form a molecular "wall" that helps confine ingrowing olfactory axons within the ONL at the outer edge of the astroglial territory. We suggest that the astroglia do not precisely regulate the specific shape of the glomeruli, but rather play a fundamental role in directing the gross position at which formation of the synaptic glomeruli will occur.