Molecular mechanisms of columnar unit formation by differential cell adhesion in the brain

脑内细胞粘附差异形成柱状单位的分子机制

基本信息

批准号：
17J09505
负责人：
Trush Olena
金额：
$ 1.09万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2017
资助国家：
日本
起止时间：
2017-04-26 至 2019-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17J09505/
关键词：
columnar structures N-cadherin DAH Drosophila visual system Differential Adhesion Flamingo columnar units

项目摘要

Columnar structure is a basic unit of the brain, but the mechanism of column formation remains largely unknown. In this study, we proposed the mechanism of column organization based on the differential level of adhesion between essential columnar neurons in the fly brain, regulated by cell adhesion molecules N-cadherin (N-cad) and Flamingo (Fmi). We revealed that column formation is initiated by three core neurons, R8, R7, and Mi1, and demonstrated that Ncad-dependent relative adhesiveness of these columnar neurons regulates their relative location within a column according to the differential adhesion hypothesis (DAH). First, we examined the level of Ncad in each of these neurons and found that columnar neurons contain more Ncad in the order of R7 > R8 > Mi1. Then, we decreased the level of Ncad in the most adhesive R7 neurons and found that the R7 expands from the center of the column to the peripheral area of the column. When Ncad level was reduced in R8 neurons, similar phenotype was observed: terminals of these neurons expanded and redirected to the peripheral area outside the column. In the contrary, overexpression of Ncad in less adhesive Mi1 neurons induced the redirection of these neurons toward the column center. Ncad overexpression in R8 neurons led to the extensive projection of R8 terminals to the center of the column. In addition, we established a mathematical model that confirms that the arrangement of core columnar neurons can be achieved solely by the differential adhesion between these core columnar neurons.

柱状结构是大脑的基本单位，但柱状结构的形成机制仍然很大程度上未知。在本研究中，我们基于果蝇大脑中必需柱状神经元之间粘附水平的差异提出了柱组织机制，该机制受到细胞粘附分子 N-钙粘蛋白 (N-cad) 和火烈鸟 (Fmi) 的调节。我们揭示了柱状形成是由三个核心神经元 R8、R7 和 Mi1 启动的，并证明这些柱状神经元的 Ncad 依赖性相对粘附性根据差异粘附假设 (DAH) 调节它们在柱内的相对位置。首先，我们检查了每个神经元中 Ncad 的水平，发现柱状神经元含有更多的 Ncad，顺序为 R7 > R8 > Mi1。然后，我们降低了粘附性最强的 R7 神经元中 Ncad 的水平，发现 R7 从柱的中心扩展到柱的外围区域。当 R8 神经元中的 Ncad 水平降低时，观察到类似的表型：这些神经元的末端扩张并重定向到柱外的外围区域。相反，在粘附性较低的 Mi1 神经元中 Ncad 的过度表达诱导这些神经元向柱中心重定向。 R8 神经元中 Ncad 的过度表达导致 R8 末端广泛投射到柱的中心。此外，我们建立了一个数学模型，证实核心柱状神经元的排列可以仅通过这些核心柱状神经元之间的差异粘附来实现。