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

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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.