Multidimensional investigation of cellular dynamics and lineage relationships in the vertebrate neural tube

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Embryonic development relies on multipotent cells producing distinct cell types in a spatially and temporally organised manner.Understanding cellular lineage - the history and relationships between cells in a tissue - establishes a framework to explaindevelopment and to explore the interplay between extrinsic signals and intrinsic competence in the generation of cellular diversity.This is particularly relevant in the vertebrate spinal cord, where recent analyses have revealed even greater molecular andorganisational complexity than previously appreciated. However, lineage relationships between different cell types in the spinal cordremain poorly characterized, as well as the relative contribution of intrinsic versus extrinsic mechanisms to cell fate decisions. Recentlydeveloped imaging- and sequencing-based lineage tracing techniques now offer the unique opportunity to address this question atan unprecedented resolution. I will perform in vivo whole-genome barcoding followed by single-cell transcriptomics to characterizethe ontogeny of neurons and glial cells. I will then use high-resolution live imaging in chick embryos to track lineage trajectoriesunfolding in real-time and obtain a detailed understanding of cellular behaviour. I will integrate these data to build a comprehensivemap of lineage relationships and cell identity acquisition in the neural tube. Moreover, these approaches are compatible withsimultaneous molecular perturbations, allowing me to test the plasticity of progenitors' potential. By combining this approach with anovel method to label unperturbed neighbouring cells, I will investigate the robustness of the system, as well as the effect of cell nonautonomousmechanisms on cell fate. Together, this will provide insight into molecularly, spatially, and temporally defined in vivolineage relationships, establishing a foundation for comparative evolutionary studies and the investigation of developmentaldisorders.