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Title: Origin and specification of cortical and hippocampal interneurons
Author: Asgarian, Zeinab
ISNI:       0000 0004 7660 8303
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available