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Origin and specification of cortical and hippocampal interneurons

Asgarian, Zeinab; (2019) Origin and specification of cortical and hippocampal interneurons. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Cortical interneurons (CINs) are generated from proliferative subcortical regions and migrate into the cortex during embryogenesis. The identity of CINs is specified through transcriptional programs initiated at the time when these cells are born and executed throughout development and maturation. The Medial and Caudal ganglionic eminences (MGE and CGE) give rise to the majority of CINs. The MGE produces the two major subtypes of CINs that express SST and PV, respectively. Previous work in the Kessaris lab had identified two non-DNA-binding transcriptional cofactor-encoding genes, Mtg8 and Mtg16, as being enriched in a subset of developing MGE-derived CINs. Here, I report that MTG8 and MTG16 have distinct expression patterns in the developing CINs and in their absence, mutant mice show deficits in CIN development. Particularly, MTG8 has important role in the correct specification and consequent survival of SST CINs. Also, ectopic expression of MTG8 interferes with PV IN specification. Interestingly, MTG8 is also expressed in projection neurons and mouse embryos lacking MTG8 also show absence of the Anterior Commissure (AC), one of the major commissures in the forebrain. I show that MTG8 expression is a novel factor required for the development of the anterior and posterior limbs of the AC. Recent data suggested that hippocampal SST INs, unlike their cortical counterparts, have a dual origin in the MGE and CGE. Using mouse genetic fate-mapping tools, I present evidence that supports a single origin of all hippocampal SST INs and argue that the subset of SST cells that were thought to be derived from CGE are likely to originate within the dorsal part of the MGE.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Origin and specification of cortical and hippocampal interneurons
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10067856
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