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

前脑发育的一个重要步骤是建立固定的背侧丘脑(产生皮层兴奋性投射神经元)和腹侧大脑皮层下(产生所有端脑抑制性中间神经元)。这决定了前体细胞的初始兴奋/抑制平衡，并强加了大脑半球的未来大小。尽管控制这种DV组织和驱动分化和形态发生的下游效应器的信号在脊椎动物中是保守的，但对于这些参与者在不同物种之间的时空调节知之甚少。然而，这种调节是大脑复杂性进化分化的马达。本项目旨在了解端脑早期发育过程中信号网络的时空演变规律。在CH的指导下，学生将分析斑马鱼、小鼠和人类端脑从神经闭合开始到神经发生早期沿DV轴的HH和Wnt信号活动的动态。这项工作将结合原位染色和转录，从组织和从老鼠和人类3D培养的数据集。3D培养将使用由BN团队优化的生物材料(冷冻胶)暴露在极化信号(HH或WNT)中。在ZH的监督下，数据集将被用来识别描述发挥作用的信令网络的中央组件的受限参数集，并构建时空端脑DV组织的动态模型。这个模型将产生上述三个物种的行为，并提供对整个进化过程中信号动态的预测。这些预测中的一些将由CH实验室的学生通过在小鼠和鱼身上进行组织染色和功能实验来验证。提案的两个方面将并行运行，将带来新的发现，并开发实践/理论动态框架，将对发育神经科学领域产生持久的影响。

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.