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Title: Role of neuro-mesodermal progenitors in neural tube formation
Author: Mugele, Dorothee
ISNI:       0000 0004 7660 5583
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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It has long been thought that neural tube and somites derive from different germ layers, namely the ectoderm and mesoderm. This paradigm was challenged by the discovery of a dual-fated cell population in the mammalian tail bud, the so-called neuro-mesodermal progenitors (NMPs), which give rise to both neuroepithelium and paraxial mesoderm beyond the gastrulation stage. The aim of this PhD thesis was to characterise how NMPs contribute to neural tube formation using mouse embryos as a model system. First, the colonisation of the neural tube by NMPs and related cell populations was studied by labelling with the green fluorescent dye DiO followed by whole-embryo culture. Cells labelled caudal to the node (the NMP location) predominantly colonised the dorsal and dorso-lateral neural tube, but not the ventral domain, which was populated from the node, the node-streak border, and anterior to the node. Next, laser-ablation was used to study the developmental requirement for NMPs. As expected, ablation of the NMP location considerably disturbed the formation of paraxial mesoderm and neuroepithelium, although this effect was only transient, as adjacent cells rapidly re-populated the ablated region. A prevailing assumption is that NMPs co-express the neural marker Sox2 and the mesodermal marker T. However, lineage tracing experiments revealed that the contribution of Sox2-expressing cells to the paraxial mesoderm at post-epiblast stages is very infrequent, whereas descendants of T-expressing cells extensively colonise both neural tube and somites. This suggested that NMPs are actually Sox2-negative. Indeed, when Sox2 was specifically depleted in the T-expressing lineage, the resulting embryos had no mesoderm defect, but substantially reduced Sox2 mRNA and protein levels in the neural tube with otherwise normal morphology and gene expression domains. This indicates that Sox2 is not specifically required for neural tube formation and that bi-potent NMPs likely do not express Sox2.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available