Arx homeobox gene is essential for development of mouse olfactory system
Arx homeobox gene is essential for development of mouse olfactory system
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DOI：
10.1242/dev.01619
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发表时间：
2005-02-01
期刊：
影响因子：
4.6
通讯作者：
Yoshihara, Y
中科院分区：
文献类型：
--
作者：
Yoshihara, S;Omichi, K;Yoshihara, Y
嗅觉系统为研究细胞增殖、迁移、分化、轴突导向、树突形态发生和突触形成提供了极好的模型。我们在这里报告的关键作用的Arx同源异型盒基因在发展中的嗅觉系统，通过分析其突变的表型。Arx蛋白在嗅球的中间神经元中表达较强，在嗅球的放射状胶质细胞中表达较弱，但在嗅感觉神经元和嗅球投射神经元中均不表达。Arx缺陷小鼠在发育的嗅觉系统中表现出严重的解剖异常：（1）嗅球的尺寸减小，（2）中间神经元祖细胞的增殖减少和进入嗅球的能力受损，（3）酪氨酸羟化酶阳性肾小球周围细胞的损失，（4）嗅球的层结构的解体，（5）嗅感觉神经元的异常轴突终止在一种不寻常的轴突缠结结构中，即纤维细胞团。因此，Arx不仅需要适当的发育过程中的Arx表达的中间神经元，但也通过影响Arx非表达的感觉神经元和投射神经元的功能性嗅觉神经回路的建立。这些研究结果表明，Arx在调节嗅球中产生的推定的指导性信号的表达，以适当的神经支配嗅觉感觉轴突的可能作用。
The olfactory system provides an excellent model in which to study cell proliferation, migration, differentiation, axon guidance, dendritic morphogenesis, and synapse formation. We report here crucial roles of the Arx homeobox gene in the developing olfactory system by analyzing its mutant phenotypes. Arx protein was expressed strongly in the interneurons; and weakly in the radial glia of the olfactory bulb, but in neither the olfactory sensory neurons nor bulbar projection neurons. Arxdeficient mice showed severe anatomical abnormalities in the developing olfactory system: (1) size reduction of the olfactory bulb, (2) reduced proliferation and impaired entry into the olfactory bulb of interneuron progenitors, (3) loss of tyrosine hydroxylase-positive periglomerular cells, (4) disorganization of the layer structure of the olfactory bulb, and (5) abnormal axonal termination of olfactory sensory neurons in an unusual axon-tangled structure, the fibrocellular mass. Thus, Arx is required for not only the proper developmental processes of Arx-expressing interneurons, but also the establishment of functional olfactory neural circuitry by affecting Arx-non-expressing sensory neurons and projection neurons. These findings suggest a likely role of Arx in regulating the expression of putative instructive signals produced in the olfactory bulb for the proper innervation of olfactory sensory axons.