The role of Pax6 gene in vertebrate neural development

Pax6基因在脊椎动物神经发育中的作用

• 批准号: 11470002
• 负责人: OSUMI Noriko
• 金额: $ 10.82万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470002/
• 关键词: Neural development; Pax6; Telencephalon; Boundary formation; Cortex; Striatum; Cell adhesion; Cadherins; bHLH転写因子; 神経細胞分化; Notchシグナル; 介在神経細胞

During development of the brain, numerous neurons of various different types are generated and delivered at their right positions, and the axons project their own targets to make correct neuronal networks. Recent advance in developmental neurobiology has revealed that such neuronal localization and axonal projection are based on the brain patterning. Pax6 is a member of the vertebrate Pax gene family, which encode transcriptional factors. Pax6 is expressed in discrete domains in the developing forebrain, hindbrain, and spinal cord. This research project aimed to elucidate roles of Pax6 in patterning the brain at cellular and molecular levels. We obtained the following results during the period supported by this grant.1) We performed tracing of neuroepithelial cells labeled with Dil under mouse whole embryo culture, and elucidated when and how the boundary between the cortex and striatum is formed at the cellular level.2) In situ hybridization revealed exclusive expression patterns of the two members of cadherin cell adhesion molecules, Rcadherin and cadherin6, in the cortex and striatum, respectively.3) Electroporation of exogenous genes into the cultured mouse embryos demonstrated that exclusive expression patterns these cadherins play important roles in maintaining the cortex/striatum boundary.4) Tracing neuroepithelial cells in the cadherin6 knockout mice revealed that the boundary between the cortex and striatum was formed but that movement of the striatal neuroepithelial cells increased.

在大脑的发育过程中，产生了许多不同类型的神经元，并将其传递到正确的位置，轴突投射自己的目标，以形成正确的神经元网络。发育神经生物学的最新进展表明，这种神经元的定位和轴突投射是基于大脑的模式。Pax6是脊椎动物Pax基因家族的成员，编码转录因子。Pax6在发育中的前脑、后脑和脊髓中的离散域中表达。该研究项目旨在阐明Pax6在细胞和分子水平上对大脑模式化的作用。在本基金资助期间，我们获得了以下结果：1）在小鼠全胚胎培养条件下，我们对Dil标记的神经上皮细胞进行了示踪，并在细胞水平上阐明了皮质和纹状体之间的边界是何时以及如何形成的。2）原位杂交揭示了钙粘蛋白细胞粘附分子Rcadherin和cadherin 6的两个成员的独特表达模式，在皮层和纹状体，3）将外源基因电穿孔到培养的小鼠胚胎中表明，这些钙粘蛋白的排他性表达模式在维持皮质/纹状体边界中起重要作用。追踪cadherin6基因敲除小鼠的神经上皮细胞发现，皮质和纹状体之间的边界形成，但纹状体神经上皮细胞的运动增加

项目成果

Nagase,T.,Shimoda,Y.,Sanai,Y.,Nakamura,S.,Harii,K.,Osumi,N.: "Differential Expression of Two Glucuronyltransferases Synthesizing HNK-1 carbohydrate epitope in the sublineages of the rat myogenic progenitors."Mechanisms of Development. 98. 145-149 (2000)

Nagase，T.，Shimoda，Y.，Sanai，Y.，Nakamura，S.，Harii，K.，Osumi，N.：“在大鼠肌源祖细胞亚系中合成 HNK-1 碳水化合物表位的两种葡萄糖醛酸基转移酶的差异表达

Yamamoto, H., Ochiya, T., Takahama, Y., Ishii, Y., Osumi, N., Sakamoto, H., Terada, M.: "Detection of spatial localization of Hst-Fgf-4 gene expression in brain and testis from adult mice."Oncogene. 19. 3805-3810 (2000)

Yamamoto, H.、Ochiya, T.、Takahama, Y.、Ishii, Y.、Osumi, N.、Sakamoto, H.、Terada, M.：“大脑中 Hst-Fgf-4 基因表达的空间定位检测

Suzuki.R.,Shintani.T.,Sakuta,H.,Kato,A,Ohkawara,T.,Osumi,N.,. et al.: "Identification of RALDH-3, a novel retinaldehyde dehydrogenase, expressed in the ventral region of the retina."Mechanisms of Development. 98. 37-50 (2000)

铃木.R.，新谷.T.，咲田，H.，加藤，A，大河原，T.，大隅，N.，。

Torii,M.,Matsuzaki,F.,Osumi,N.,et al.: "Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system"Development. 126. 443-456 (1999)

Torii,M.、Matsuzaki,F.、Osumi,N.等人：“转录因子 Mash-1 和 Prox-1 描绘了发育中的中枢神经系统中神经干细胞分化的早期步骤”的开发。

Kawano, H., Fukuda, T., Kubo, K., Horie, M., Takeuchi, K., Osumi, N., Eto, K., and Kawamura, K.: "Pax6 is required for the thalamocortical pathway formation in fetal rats."J.Comp.Neurol.. 408. 147-60 (1999)

Kawano, H.、Fukuda, T.、Kubo, K.、Horie, M.、Takeuchi, K.、Osumi, N.、Eto, K. 和 Kawamura, K.：“Pax6 是丘脑皮质通路形成所必需的