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Resolving spinal cord cell type evolution with single cell sequencing

Project description

Insight into vertebrate spinal cord evolution

The vertebrate brain and spinal cord are characterised by an unparalleled diversity of cell types and complex mechanisms that organise them into a sophisticated network. Although the vertebrate nervous system evolved to address the enhanced sensory input and direct coordinated motor output, it is currently debated whether the theory of whole genome duplication has contributed to its complexity. To address this, the EU-funded ScLamprey project will study the spinal cord of the lamprey, one of the first branching vertebrates. Scientists will focus on the molecular mechanisms that lead to spinal cord cell specification and their evolutionary origin. The generated cellular atlas will serve as the foundation for future studies into the evolution of the vertebrate nervous system.

Objective

The emergence of vertebrates was accompanied by a major increase in nervous system complexity, as a sophisticated brain and spinal cord evolved to process enhanced sensory input and direct co-ordinated motor output. Such complexity is achieved by an increase in cell number, a greater diversity of cell types and sophisticated mechanisms to organise them. Is has long been debated whether the “2R” whole genome duplications, which occurred just before the vertebrate split, contributed to the vertebrate increased complexity. To address this, we will focus on the lamprey spinal cord –a representative of the first branching vertebrates – and relate gene duplication events to the emergence of new neural cell types. Bulk RNA sequencing and developmental studies have started to shed light on neural patterning mechanisms in lamprey, but they do not provide cellular resolution in this complex tissue. This proposal combines traditional molecular methods with cutting-edge single cell mRNA profiling, to explore (1) the cellular diversity of the lamprey spinal cord, (2) the molecular mechanisms that specify those cell types and (3) the evolutionary origins of these mechanisms. First, I will identify marker genes that define specific cell types in lamprey embryonic spinal cord. Second, I will characterise each cell type transcriptional profile at single-cell resolution. Third, I will manipulate pattering signals and assesses the effect on gene expression, particularly on 2R paralogs. Finally, I will compare the lamprey spinal cord to that of other chordates, and relate gene duplication to the evolution of new cell types.
This project will generate a cellular atlas of the lamprey spinal cord, which will be the framework for future studies, and shed light onto whether the 2R genome duplications supported the evolution of vertebrate complexity.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 224 933,76
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom
Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 224 933,76