Integration of cellular, molecular and mathematical investigation of the evolution of early telencephalon organisation

早期端脑组织进化的细胞、分子和数学研究的整合

• 批准号: 2578150
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2578150
• 关键词: Integration; cellular; molecular; mathematical; investigation

One important step in forebrain development is the establishment of a stereotyped dorsalpallium (giving rise to cortical excitatory projection neurons) and the ventral subpallium(producing all telencephalic inhibitory interneurons). This determines the initialexcitatory/inhibitory balance of progenitors and imposes the future size of the brainhemispheres.Although the signals controlling this DV organisation and the downstream effectors drivingdifferentiation and morphogenesis are conserved across vertebrates, little is known on thespatiotemporal modulation of these players across species. Yet, this modulation is a motor ofevolutionary divergence in brain complexity. This project aims to understand the evolutionaryspatiotemporal modulation of signalling networks during early telencephalon development.Under the supervision of CH, the student will analyse the dynamics of Hh and Wnt signallingactivity along the DV axis in zebrafish, mouse and human telencephalon from onset of neuralclosure to early neurogenesis. This work will combine in situ staining and transcriptomedatasets from tissue and from mouse and human 3D culture. The 3D culture will be exposedto polarised signals (Hh or Wnt) using biomaterial (cryogels) optimised by the BN team.Under ZH supervision, the datasets will be used to identify a restricted set of parametersdescribing the central components of the signalling network at play and to construct adynamic model of spatiotemporal telencephalic DV organisation. This model will generate thebehaviour of the three species characterised above as well as deliver predictions on thesignalling dynamic across evolution. Some of these predictions will then be verified by thestudent in CH lab, by tissue staining and functional experiments in mouse and fish.Both sides of the proposal will be run in parallel, will deliver novel findings and develop apractical/theoretical dynamic framework that will have a lasting impact on the field ofdevelopmental neuroscience.

前脑发育的一个重要一步是建立定型的背面（产生皮层兴奋性投射神经元）和腹侧pall体（产生所有尾脑抑制性中间神经元）。这决定了祖细胞的初始性/抑制性平衡，并施加了脑壳的未来大小。尽管控制该DV组织的信号和驱动分化和形态发生的信号在整个脊椎动物中都持续存在，但在这些播放物中的thespatiotagiotal调节中，几乎不知道这些物种。然而，这种调制是大脑复杂性进化差异的运动。该项目旨在了解早期尾脑发育过程中信号网络的进化速度时量变调节。在CH的监督下，学生将分析Zebrafish，Mouse和Humanthon telencephalon沿DV轴的HH和WNT信号，从神经神经术的发作到早期神经神经膜的发作。这项工作将结合到组织以及小鼠和人类3D培养物的原位染色和转录。 3D文化将使用BN团队优化的生物材料（冷冻凝胶）暴露于两极分化信号（HH或WNT）。在ZH的监督下，数据集将用于确定一组受限的参数集，以播放信号网络的中央组成部分，并构建了Spatiotemporempormoral Telencemalal telencephalicalic dv dv dv dv dv。该模型将产生上面表征的三个物种的行为，并在整个进化过程中提供对动态的预测。然后，其中一些预测将通过CH Lab中的thatudent进行验证，通过组织染色和小鼠和鱼类的功能实验。该提案的两侧将并行运行，将提供新的发现并发展出了超级/理论动态框架，这些框架将对开发神经科学领域产生持久影响。