Molecular Mechanism of Cortical Area Specification

皮质区域规范的分子机制

• 批准号: 16300108
• 负责人: NAKAMURA Shun
• 金额: $ 9.54万
• 依托单位: National Institute of Neuroscience, National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300108/
• 关键词: cortical area; somatosensory cortex; thalamic projection; cadherin; Shh; Fezl; whisker pattern; DNA microarray; 機能領野; 視床; ハンドシェークモデル; 細胞移動; サブプレートニューロン; Wnt; シグナル伝達; 神経科学; 脳・神経; 脳神経疾患; 発生・分化

1. The mammalian neocortex develops layer organizations with regional differences represented by expression of multiple genes at embryonic stages. These genes could play important roles in the formation of areal cyto-architecture, yet, the number of genes identified so far is not sufficient to explain such intricate processes. Here we collected five regions-the medial, dorsal, lateral, rostral and occipital from the dissected E 16.5 mouse cerebral cortex, performed extensive gene expression analysis using DNA microarray, and reached the successful identification of seven genes from the dorsal region, three genes from the medial region, and three genes from the lateral region. Particularly, all seven genes identified in the dorsal region demarcated the future somatosensory and auditory areas in the cortical plate with high rostrolateral-low caudomedial gradation. Furthermore, the regional expression pattern of NeuropeptideY was shifted rostral and the layer specificity was disorganized … More in the Pax6-deficient mice. Our results provide new information about a subclass of regionally expressed genes in the cortical plate at the late embryonic stage, which may help understand the molecular mechanisms of neocortical arealization.2. Next, we challenged the somatosensory patterning mechanism by investigating the role of a peripheral whisker pattern for the patterning of the mouse somatosensory trigeminal projection at the brainstem and thalamus. The whisker pattern was manipulated by infecting the embryonic epidermis with adenovirus harboring Shh. The ectopic expression of Shh led to the induction of extra whiskers and displacement of whiskers, where these whiskers were histologically normal. The altered whisker pattern was isomorphically represented in the brainstem (barrelette: subnuclei principalis and subnuclei interpolaris), thalamus (barreloid) and cortex (barrel). These results highlight the role of the peripheral whisker pattern for the central patterning of the brainstem, thalamus, and cortex in the mouse somatosensory system.3. Finally, we examined the thalamocortical and corticofugal pathway in developing Fezl-deficient mice (Dr. Masahiko Hibi at Riken). The fez-like (Fezl) protein is a transcriptional repressor selectively expressed in the deep layers of the developing cortex. In normal mice, cortical and thalamic axons meet in the internal capsule between embryonic day (E) 13.5 and E14.5 and fasciculate with each other as they extend to their targets, namely, the thalamus and cortex, respectively. In Fezl-deficient mice, most of the thalamic and cortical axons stop in the internal capsule and at the pallial-subpallial boundary, respectively, at E14.5. Based upon previous studies, the present study suggests that the aberrant trajectories of the thalamocortical axons in Fezl-deficient mice are caused by defects in the cortical efferent neurons that express Fezl. Less

1. 哺乳动物新皮质发育出具有区域差异的层组织，其表现为胚胎阶段多个基因的表达。这些基因可能在区域细胞结构的形成中发挥重要作用，然而，迄今为止鉴定的基因数量不足以解释这种复杂的过程。在这里，我们从解剖的E 16.5小鼠大脑皮层中收集了五个区域——内侧、背侧、外侧、头侧和枕叶，利用DNA微阵列进行了广泛的基因表达分析，成功鉴定了背侧区域的7个基因、内侧区域的3个基因和外侧区域的3个基因。特别是，在背侧区域鉴定的所有七个基因以高头外侧-低尾内侧分级划分了皮质板中未来的体感和听觉区域。此外，在 Pax6 缺陷小鼠中，NeuropeptideY 的区域表达模式发生了向喙侧转移，并且层特异性紊乱。我们的研究结果提供了关于胚胎晚期皮质板区域表达基因的一个亚类的新信息，这可能有助于理解新皮质区域化的分子机制。2．接下来，我们通过研究外周胡须模式在小鼠脑干和丘脑体感三叉神经投射模式中的作用来挑战体感模式机制。通过用携带Shh的腺病毒感染胚胎表皮来操纵胡须图案。 Shh 的异位表达导致了额外胡须的诱导和胡须的移位，而这些胡须在组织学上是正常的。改变的胡须模式在脑干（桶状：原则亚核和极间亚核）、丘脑（桶状）和皮质（桶状）中具有同构性。这些结果强调了外周胡须模式对于小鼠体感系统中脑干、丘脑和皮质的中央模式的作用。3．最后，我们检查了发育中的 Fezl 缺陷小鼠的丘脑皮质和离皮质通路（Riken 的 Masahiko Hibi 博士）。 fez 样 (Fezl) 蛋白是一种转录抑制蛋白，在发育中的皮层深层选择性表达。在正常小鼠中，皮质轴突和丘脑轴突在胚胎日 (E) 13.5 和 E14.5 之间在内囊中相遇，并在分别延伸到目标（即丘脑和皮质）时彼此束动。在 Fezl 缺陷小鼠中，大多数丘脑和皮质轴突分别停止于内囊和大脑皮层-大脑皮层下边界，即 E14.5。基于之前的研究，本研究表明 Fezl 缺陷小鼠中丘脑皮质轴突的异常轨迹是由表达 Fezl 的皮质传出神经元的缺陷引起的。较少的

项目成果

Defects in reciprocal projections between the thalamus and cerebral cortex in the early development of Fezl-deficient mice

• DOI: 10.1002/cne.21401
• 发表时间: 2007-07-20
• 期刊: JOURNAL OF COMPARATIVE NEUROLOGY
• 影响因子: 2.5
• 作者: Komuta, Yukari;Hibi, Masahiko;Kawano, Hitoshi
• 通讯作者: Kawano, Hitoshi

TrkB-T1 regulates the RhoA signaling and actin cytoskeleton in glioma cells

• DOI: 10.1016/j.bbrc.2006.02.033
• 发表时间: 2006-04-14
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Ohira, K;Homma, KJ;Hayashi, M
• 通讯作者: Hayashi, M

Gene expression analysis of the late embryonic mouse cerebral cortex using DNA microarry : identification of several region-and layer-specific genes.

使用 DNA 微阵列对晚期胚胎小鼠大脑皮层进行基因表达分析：鉴定几个区域和层特异性基因。

• 发表时间: 2004
• 期刊: Cerebral Cortex 14
• 作者: A Matsuo;JP Bellier;T Hisano;Y Aimi;O Yasuhara;I Tooyama;N Saito;H Kimura;竹中克行;Funatsu N
• 通讯作者: Funatsu N

BDNF regulates the maturation of layer 4 fast spiking cells after the 2nd postnatal week in the developing barrel cortex

BDNF 在出生后第 2 周后调节发育中的桶状皮质中第 4 层快速尖峰细胞的成熟

• 发表时间: 2007
• 作者: C Itami;F Kimura;S Nakamura
• 通讯作者: S Nakamura