Ogawa Yasuhiro, Takebayashi Hirohide, Takahashi Masanori, Osumi Noriko, Iwasaki Yasuno, Ikenaka Kazuhiro
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Japan.
Dev Neurosci. 2005;27(6):364-77. doi: 10.1159/000088452.
The central nervous system of the mammalian embryo is organized according to the expression of region-specific transcription factors along the anteroposterior and/or the dorsoventral axis. For example, the dorsal ventricular zone (VZ) of the embryonic spinal cord expresses Pax3 and Pax7, the ventral VZ expresses Pax6, and the more ventral VZ expresses Nkx2.2. Properties of neuronal precursors located in the VZ are determined by the characteristic expression patterns of these transcription factors, leading to the generation of distinct classes of neurons. Recent studies demonstrated that radial glial cells produce neurons in addition to glia during central nervous system development. Thus, neuronal precursor diversity may be dependent upon the diversity of radial glial cells. To investigate this hypothesis, we analyzed the expression of radial glial cell markers and transcription factors in the mouse embryonic spinal cord. We show that radial glial cells indeed express domain-specific transcription factor. Moreover, they varied in expression of the astrocyte-specific glutamate transporter. The region where the astrocyte-specific glutamate transporter is strongly expressed in the ventral radial glial cells is closely related to the Pax6-expressing domain, and the weakly expressing region corresponding to the Nkx2.2-expressing domain. Furthermore, dorsal radial fibers expressed ephrin-B1. Thus, different types of radial glial cells exist in different domains defined by the transcription factor expression at E12.5. We also show that this diversity continues to the gliogenic stage of radial glial cells. This raises the idea that astrocytes generated from different domains along the dorsoventral axis in the mouse spinal cord have distinct characteristics.
哺乳动物胚胎的中枢神经系统是根据沿前后轴和/或背腹轴的区域特异性转录因子的表达来组织的。例如，胚胎脊髓的背侧脑室区（VZ）表达Pax3和Pax7，腹侧VZ表达Pax6，更腹侧的VZ表达Nkx2.2。位于VZ的神经元前体的特性由这些转录因子的特征性表达模式决定，从而导致不同类型神经元的产生。最近的研究表明，在中枢神经系统发育过程中，放射状胶质细胞除了产生胶质细胞外还能产生神经元。因此，神经元前体的多样性可能取决于放射状胶质细胞的多样性。为了研究这一假设，我们分析了小鼠胚胎脊髓中放射状胶质细胞标志物和转录因子的表达。我们发现放射状胶质细胞确实表达区域特异性转录因子。此外，它们在星形胶质细胞特异性谷氨酸转运体的表达上存在差异。星形胶质细胞特异性谷氨酸转运体在腹侧放射状胶质细胞中强烈表达的区域与表达Pax6的区域密切相关，而弱表达区域则对应于表达Nkx2.2的区域。此外，背侧放射状纤维表达ephrin-B1。因此，在E12.5时，由转录因子表达定义的不同区域存在不同类型的放射状胶质细胞。我们还表明，这种多样性持续到放射状胶质细胞的胶质生成阶段。这就提出了一个观点，即小鼠脊髓中沿背腹轴不同区域产生的星形胶质细胞具有不同的特征。
