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Title: Origin and specification of cortical interneurons in the mouse subpallium
Author: Rubin, A.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Cortical GABAergic interneurons are intimately involved in modulating the function of the complex circuitry of the cortex and show a wealth of different forms. Identifying these forms and unravelling the developmental pathways that specify them will provide us with greater insight into cortical function and neurodevelopmental disorders including epilepsy, autism and schizophrenia. Interneurons are generated in the progenitor regions of the subcortical (or subpallial) forebrain and migrate into the cortex during embryonic development. The subpallial progenitor zones can be broadly divided into the lateral, medial and caudal ganglionic eminences (LGE, MGE and CGE, respectively), the pre-optic area (POA) and the septum. Of these, the MGE, POA and CGE have been identified as sources of cortical interneurons. MGE- and POA-derived interneurons have been fate-mapped using genetic lineage tracing. In order to fate-map the LGE/CGE, we developed a novel subtractive labelling method. We generated a BAC transgenic mouse expressing a floxed Venus reporter gene under the transcriptional control of Dlx1 (Dlx1-Venusfl). Dlx1-Venusfl mice express the yellow fluorescent protein in all subcortical progenitor regions in the embryo and nearly 100% of adult cortical interneurons. To selectively label LGE/CGE-derived interneurons we crossed the Dlx1-Venusfl mice with the Nkx2.1-Cre and Lhx6-Cre BAC transgenic mouse lines. We found that the LGE/CGE and MGE give rise to distinct subtypes of interneurons, pointing to differences in the genetic programs driving their specification and development. In order to identify such programs, I used Dlx1-Venusfl/Nkx2.1-CreTg and Nkx2.1-CreTg/Rosa26-GFP mice to purify LGE/CGE- and MGE-derived cortical interneurons, respectively, using fluorescence-activated cell sorting. Analysis of their gene expression profiles by RNA microarray analysis identified a number of genes that are differentially expressed between these two populations. I focused briefly on a gene called Prox1 as a candidate transcriptional modulator of LGE/CGE-derived cortical interneuron development.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available