Multidimensional investigation of cellular dynamics and lineage relationships in the vertebrate neural tube
Lead Research Organisation:
The Francis Crick Institute
Department Name: Research
Abstract
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 explain
development 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 and
organisational complexity than previously appreciated. However, lineage relationships between different cell types in the spinal cord
remain poorly characterized, as well as the relative contribution of intrinsic versus extrinsic mechanisms to cell fate decisions. Recently
developed imaging- and sequencing-based lineage tracing techniques now offer the unique opportunity to address this question at
an unprecedented resolution. I will perform in vivo whole-genome barcoding followed by single-cell transcriptomics to characterize
the ontogeny of neurons and glial cells. I will then use high-resolution live imaging in chick embryos to track lineage trajectories
unfolding in real-time and obtain a detailed understanding of cellular behaviour. I will integrate these data to build a comprehensive
map of lineage relationships and cell identity acquisition in the neural tube. Moreover, these approaches are compatible with
simultaneous molecular perturbations, allowing me to test the plasticity of progenitors' potential. By combining this approach with a
novel method to label unperturbed neighbouring cells, I will investigate the robustness of the system, as well as the effect of cell nonautonomous
mechanisms on cell fate. Together, this will provide insight into molecularly, spatially, and temporally defined in vivo
lineage relationships, establishing a foundation for comparative evolutionary studies and the investigation of developmental
disorders.
Understanding cellular lineage - the history and relationships between cells in a tissue - establishes a framework to explain
development 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 and
organisational complexity than previously appreciated. However, lineage relationships between different cell types in the spinal cord
remain poorly characterized, as well as the relative contribution of intrinsic versus extrinsic mechanisms to cell fate decisions. Recently
developed imaging- and sequencing-based lineage tracing techniques now offer the unique opportunity to address this question at
an unprecedented resolution. I will perform in vivo whole-genome barcoding followed by single-cell transcriptomics to characterize
the ontogeny of neurons and glial cells. I will then use high-resolution live imaging in chick embryos to track lineage trajectories
unfolding in real-time and obtain a detailed understanding of cellular behaviour. I will integrate these data to build a comprehensive
map of lineage relationships and cell identity acquisition in the neural tube. Moreover, these approaches are compatible with
simultaneous molecular perturbations, allowing me to test the plasticity of progenitors' potential. By combining this approach with a
novel method to label unperturbed neighbouring cells, I will investigate the robustness of the system, as well as the effect of cell nonautonomous
mechanisms on cell fate. Together, this will provide insight into molecularly, spatially, and temporally defined in vivo
lineage relationships, establishing a foundation for comparative evolutionary studies and the investigation of developmental
disorders.
Organisations
Publications
Frith TJR
(2024)
From signalling to form: the coordination of neural tube patterning.
in Current topics in developmental biology