Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord
Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord
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DOI：
10.1111/j.1460-9568.2007.05906.x
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发表时间：
2007-12-01
影响因子：
3.4
通讯作者：
Kiehn, Ole
中科院分区：
文献类型：
--
作者：
Lundfald, Line;Restrepo, C. Ernesto;Kiehn, Ole
腹侧脊髓由沿背腹侧轴的不同的、遗传上确定的祖域产生的中间神经元群组成。许多中间神经元群位于哺乳动物的脊髓腹侧，那里包含运动的中枢模式发生器。为了更好地理解运动网络，我们使用不同的转基因小鼠对这些中间神经元组中的一个进行解剖表征，称为V2中间神经元。这组神经元要么是有丝分裂后表达转录因子Chx10的V2a中间神经元，要么是表达转录因子Gata2和Gata3的V2b中间神经元。我们发现所有的V2a和大部分V2b中间神经元在胚胎和新生儿中都是同侧突起的。V2a中间神经元以谷氨酸能为主，V2b中间神经元以氨基丁酸能或甘氨酸能为主。此外，我们证明了很大比例的V2中间神经元表达轴突引导分子EphA4，该分子先前被证明对运动网络的正确组织很重要。我们还发现，单独的V2中间神经元和运动神经元并不能解释脊髓中所有表达epha4的神经元。总之，这些发现能够更好地解释运动背后的神经网络，并开辟了对哺乳动物中枢模式生成器的未知组成部分的研究。
The ventral spinal cord consists of interneuron groups arising from distinct, genetically defined, progenitor domains along the dorsoventral axis. Many of these interneuron groups settle in the ventral spinal cord which, in mammals, contains the central pattern generator for locomotion. In order to better understand the locomotor networks, we have used different transgenic mice for anatomical characterization of one of these interneuron groups, called V2 interneurons. Neurons in this group are either V2a interneurons marked by the postmitotic expression of the transcription factor Chx10, or V2b interneurons which express the transcription factors Gata2 and Gata3. We found that all V2a and most V2b interneurons were ipsilaterally projecting in embryos as well as in newborns. V2a interneurons were for the most part glutamatergic while V2b interneurons were mainly GABAergic or glycinergic. Furthermore, we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4-expressing neurons in the spinal cord. Together, these findings enable a better interpretation of neural networks underlying locomotion, and open up the search for as yet unknown components of the mammalian central pattern generator.