Understanding gene regulation mechanisms that underlie generation of interneuron diversity

Eugene Makeyev (primary)
Centre for Developmental Neurobiology
King's College London
Oscar Marin (secondary)
Centre for Developmental Neurobiology
King's College London


Brain function requires multiple types of neurons characterised by distinctive structural, molecular and physiological features. How this diversity emerges from a smaller number of progenitor states is a fascinating biological problem. This project will elucidate gene regulation networks allowing neural stem cells to differentiate into different types of cortical interneurons. It will combine advanced computational analyses of single-cell gene expression data with experimental validation of predicted regulators using cutting-edge in vitro and in vivo approaches. We expect to uncover novel mechanisms underlying nervous system development and devise new stem cell-based protocols for generating specific types of interneurons in vitro.


1. Yap K, Xiao Y, Friedman BA, Je HS, and Makeyev EV (2016) Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms. Cell Rep. 15:1316-1328. https://doi.org/10.1016/j.celrep.2016.04.012

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. Yap K, Mukhina S, Zhang G, Tan JSC, Ong HS, and Makeyev EV (2018) A Short Tandem Repeat-Enriched RNA Assembles a Nuclear Compartment to Control Alternative Splicing and Promote Cell Survival. Mol Cell 72:525-540. https://doi.org/10.1016/j.molcel.2018.08.041

4. 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

5. Yap K, Lim ZQ, Khandelia P, Friedman B, Makeyev EV. (2012) Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention. Genes Dev 26:1209-1223. https://doi.org/10.1101/gad.188037.112

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