Cell Shape and the Formation of Macro Cellular Assemblies During Embryo Development

胚胎发育过程中细胞形状和宏观细胞组件的形成

• 批准号: 1754546
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1754546
• 关键词: Cell; Shape; Formation; Macro; Cellular; Cell; Shape; Formation; Macro; Cellular

The developing central nervous system is composed of many macrocellular assemblies of neurons that receive similar synaptic inputs and have similar axonal outputs. These so-called neuronal nuclei display a diverse set of shapes, ranging from ovoid and allantoid shapes to crescents and laminae. Over the past decade, we have shown that members of the cadherin family of cell adhesion molecules play roles critical to the formation of macro cellular assemblies of motor neurons in the brainstem and spinal cord. This cadherin expression is combinatorial in nature and drives specificity of cellular assembly, although the precise details of cadherin presentation within an individual cell and how this drives specificity are not known. Recently, we have found that a neuronal nucleus involved in sound source localization also utilizes cadherin function to form. However, this nucleus forms a lamina shape and some preliminary static modelling that we have performed suggests that the shape of the neurons in the nucleus drives formation of the lamina via cadherin function. This PhD project seeks to use mathematical models to understand how cell shape changes could influence formation of neuronal assemblies via adhesion mechanisms and to take the results of this modelling in vivo and in vitro to understand better how cadherin-based adhesion could drive the formation of different three dimensional shapes of neuronal nuclei. We shall focus the project initially on motor and auditory nuclei as well as the brainstem nuclei that process visual information, which form a nested curved layered structure. These experiments will be performed both in silico as well as in vivo in chicken and quail embryos and in reduced tissue culture experiments using either cell lines or primary populations of developing neurons. The techniques used include cell culture, in ovo electroporation, in situ hybridisation and immunofluorescence microscopy on thin tissue sections. There may also be an opportunity to do time-lapse imaging on thick sections of the cultured brainstem.

发育中的中枢神经系统由许多接收类似突触输入并具有相似轴突输出的神经元的大细胞组成组成。这些所谓的神经元核表现出各种形状，范围从卵形和甲状腺素形状到新月形和薄片。在过去的十年中，我们已经表明，细胞粘附分子家族的成员在脑干和脊髓中运动神经元的宏细胞组件至关重要。这种钙粘蛋白的表达本质上是组合的，并驱动了细胞组装的特异性，尽管单个细胞内的钙粘蛋白表现的精确细节以及该驱动特异性如何尚不清楚。最近，我们发现参与声源定位的神经元核也利用钙粘着蛋白功能形成。然而，该核形成了我们执行的椎板形状和一些初步的静态建模，这表明核中神经元的形状通过钙粘着蛋白功能驱动层形成。该博士学位项目试图使用数学模型来了解细胞形状的变化如何通过粘附机制影响神经元组件的形成，并在体内和体外进行这种建模的结果，以更好地了解基于钙粘着蛋白的粘附如何驱动神经元核的不同三维形状的形成。我们将最初将项目集中在运动和听觉核以及处理视觉信息的脑干核上，该核形成了嵌套弯曲的分层结构。这些实验将在鸡和鹌鹑胚胎中以及使用发育中神经元的细胞系或原发性种群中进行的鸡和鹌鹑胚胎中的体内进行。所使用的技术包括细胞培养，在OVO电穿孔中，原位杂交和薄组织切片上的免疫荧光显微镜。也可能有机会对培养的脑干的厚部分进行延时成像。