Takahashi Kaoru, Liu Fu-Chin, Hirokawa Katsuiku, Takahashi Hiroshi
Developmental Neurobiology Group, Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan.
J Neurosci Res. 2003 Jul 1;73(1):61-72. doi: 10.1002/jnr.10638.
Many members of the forkhead/winged helix transcriptional factors are known to be regulators of embryogenesis. Mutations of the Fox gene family have been implicated in a range of human developmental disorders. Foxp2, a member of the Fox gene family, has recently been identified as the first gene that is linked to an inherited form of language and speech disorder. To elucidate the anatomical basis of language processing in the brain, we have examined the expression pattern of Foxp2 gene and its homologous gene, Foxp1, in the rat brain through development. Expression of Foxp2 mRNA was detected in the ventral telencephalon as early as embryonic day 13. Foxp2 mRNA was expressed primarily in differentiated cells of the lateral ganglionic eminence (striatal primordium). Of particular interest was that the developmental expression of Foxp2 followed a compartmental order in the striatum. Patches containing high levels of Foxp2 were aligned with patches enriched in mu-opoid receptor, a marker for striosomal cells, in the striatum through postnatal development. Conversely, Foxp2-positive patches were devoid of calbindin-D28k, a maker for striatal matrix cells. Therefore, Foxp2 was preferentially expressed in striosomal compartment in the striatum during development. In the mature striatum, Foxp2 expression was maintained in striosomes, although its expression level was reduced. In contrast to Foxp2, Foxp1 was expressed in both the striosomal and matrix compartments in the striatum through development. The striatum is known to be involved in the process of procedural memory, and mutation of Foxp2 results in neurological disorders of language and speech. Given the preferential expression of Foxp2 in the striosomal compartment, the striatum, particularly the striosomal system, may participate in neural information processing for language and speech. Our suggestion is consistent with the declarative/procedural model proposed by Ullman and colleagues (Ullman et al. [1997] J. Cogn. Neurosci. 9:266-276; Ullman [2001] Nat. Rev. Neurosci. 2:717-726), in which the procedural memory-dependent mental grammar is rooted in the basal ganglia and the frontal cortex and the declarative memory-dependent mental lexicon is rooted in the temporal lobe.
已知许多叉头框/翼状螺旋转录因子成员是胚胎发育的调节因子。Fox基因家族的突变与一系列人类发育障碍有关。Foxp2是Fox基因家族的成员，最近被确定为第一个与遗传性语言和言语障碍相关的基因。为了阐明大脑中语言处理的解剖学基础，我们研究了Foxp2基因及其同源基因Foxp1在大鼠大脑发育过程中的表达模式。早在胚胎第13天，就在腹侧端脑中检测到了Foxp2 mRNA的表达。Foxp2 mRNA主要在外侧神经节隆起（纹状体原基）的分化细胞中表达。特别有趣的是，Foxp2在纹状体中的发育表达遵循一种分区顺序。在出生后的发育过程中，含有高水平Foxp2的斑块与富含μ-阿片受体（一种纹状体小体细胞标记物）的斑块在纹状体中排列在一起。相反，Foxp2阳性斑块缺乏钙结合蛋白-D28k（一种纹状体基质细胞标记物）。因此，在发育过程中，Foxp2在纹状体的纹状体小体区优先表达。在成熟的纹状体中，Foxp2的表达在纹状体小体中得以维持，尽管其表达水平有所降低。与Foxp2不同，Foxp1在发育过程中在纹状体的纹状体小体和基质区均有表达。已知纹状体参与程序性记忆过程，而Foxp2的突变会导致语言和言语方面的神经障碍。鉴于Foxp2在纹状体小体区的优先表达，纹状体，尤其是纹状体小体系统，可能参与语言和言语的神经信息处理。我们的观点与Ullman及其同事提出的陈述性/程序性模型（Ullman等人，[1997]《认知神经科学杂志》9:266 - 276；Ullman，[2001]《自然神经科学评论》2:717 - 726）一致，在该模型中，依赖程序性记忆的心理语法植根于基底神经节和额叶皮层，而依赖陈述性记忆的心理词汇表植根于颞叶。
