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Title: Generation of neuronal diversity in the mammalian cerebral cortex
Author: Llorca Molina, Alfredo
ISNI:       0000 0004 9357 5822
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2020
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The mammalian cerebral cortex is one of the most complex cellular machineries developed by nature, containing a wide diversity of neuronal cell types that present unique structural and functional features. These diverse cell types are, moreover, heterogeneously distributed across different regions of the cortical territory, assembling region-specific cellular architectures. Despite decades of study, the developmental mechanisms that originate this diversity are not completely understood. In this thesis, I have studied the mechanisms underlying the origin of the diverse types of excitatory pyramidal cells and inhibitory interneurons that populate the murine cortex. Our results indicate that cortical progenitor cells exhibit heterogeneous neurogenic behaviours, generating progenies composed by a wide range of sizes and fates. These results are compatible with a stochastic model of cortical neurogenesis, in which cortical progenitor cells, despite sharing common molecular programmes, undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Such mechanism would allow the flexible tuning of the neuronal output of cortical progenitor cells, supporting the generation of diverse region-specific cytoarchitectures without the requirement of region-specific intrinsic programmes. We also investigated the mode of division of progenitor cells in the embryonic subpallium. Our observations suggest the existence of expansive intermediate progenitor cells in the medial ganglionic eminence, which divide several times to produce small groups of post-mitotic neurons. Finally, we designed and tested a novel high-resolution lineage tracing method that will allow us to map interneuron origins from development to adult life. Used in appropriate experimental conditions, this method will represent a powerful tool for the identification of interneurons derived from individual progenitor cells. This tool will open the opportunity for an in-depth description of the neuronal outputs of subpallial progenitor cells at single cell resolution.
Supervisor: Marin Parra, Oscar ; Rico Gozalo, Beatriz Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available