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

One important step in forebrain development is the establishment of a stereotyped dorsal
pallium (giving rise to cortical excitatory projection neurons) and the ventral subpallium
(producing all telencephalic inhibitory interneurons). This determines the initial
excitatory/inhibitory balance of progenitors and imposes the future size of the brain
hemispheres.
Although the signals controlling this DV organisation and the downstream effectors driving
differentiation and morphogenesis are conserved across vertebrates, little is known on the
spatiotemporal modulation of these players across species. Yet, this modulation is a motor of
evolutionary divergence in brain complexity. This project aims to understand the evolutionary
spatiotemporal modulation of signalling networks during early telencephalon development.
Under the supervision of CH, the student will analyse the dynamics of Hh and Wnt signalling
activity along the DV axis in zebrafish, mouse and human telencephalon from onset of neural
closure to early neurogenesis. This work will combine in situ staining and transcriptome
datasets from tissue and from mouse and human 3D culture. The 3D culture will be exposed
to 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 parameters
describing the central components of the signalling network at play and to construct a
dynamic model of spatiotemporal telencephalic DV organisation. This model will generate the
behaviour of the three species characterised above as well as deliver predictions on the
signalling dynamic across evolution. Some of these predictions will then be verified by the
student 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 a
practical/theoretical dynamic framework that will have a lasting impact on the field of
developmental neuroscience.