Gene regulation of developmental interneuron diversification

Oscar Marín (primary)
Developmental Neurobiology
King's College London
Nicholas Luscombe (secondary)
Genetics, Evolution & Environment
UCL

Abstract

GABAergic interneurons in the cerebral cortex have evolved as a highly heterogeneous collection of cell types. Current estimates suggest that up to 60 different types of interneurons may populate the cortex, but the mechanisms underlying their generation remain unclear. This project will investigate the developmental diversification of a class of cortical interneurons characterised by the early expression of the neuropeptide SST. We will use advanced computational analyses of single-cell gene expression data to identify the developmental trajectories underlying cell diversification within this group of interneurons. We will then use in vivo approaches to test the role of differentially expressed genes in the specialisation of distinct interneuron cell types. We expect to uncover novel mechanisms underlying cell type specification in the nervous system.


References

1. Lim L, Mi D, Llorca A, and Marín O (2018) Development and Functional Diversification of Cortical Interneurons. Neuron100:294-313. https://doi.org/10.1016/j.neuron.2018.10.009

2. Mi D, Li Z, Lim L, Li M, Moissidis M, Yang Y, Gao T, Hu TX, Pratt T, Price DJ, Sestan N, and Marín O (2018) Early emergence of cortical interneuron diversity in the mouse embryo. Science 360, 81-85. https://doi.org/10.1126/science.aar6821

3. Mayer C, Hafemeister C, Bandler RC, Machold R, Batista Brito R, Jaglin X, Allaway K, Butler A, Fishell G, and Satija, R (2018) Developmental diversification of cortical inhibitory interneurons. Nature 555, 457-462. https://doi.org/10.1038/nature25999

4. Ghahramani A, Watt FM, and Luscombe NM (2018). Generative adversarial networks simulate gene expression and predict perturbations in single cells. bioRxiv preprint. https://doi.org/10.1101/262501

5. Tian et al (2019). Benchmarking single cell RNA-sequencing analysis pipelines using mixture control experiments. Nature Methods (preprint ahead of publication). https://doi.org/10.1038/s41592-019-0425-8


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
DevelopmentNeurobiology
Techniques & Approaches
BioinformaticsEngineeringGeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology