Identification of neurogenic fate determinants aiming to prolong cortical neurogenesis

Vierl, Franziska (2021): Identification of neurogenic fate determinants aiming to prolong cortical neurogenesis. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)

Abstract

During neocortical development, neural stem cells undergo several fate switches necessary for a proper sequential progression through a proliferative, neurogenic and finally gliogenic phase. While some of the fate determining factors have already been examined, others are poorly described, and many may not have been identified as such yet at all. In this thesis, I propose a role of the NuRD complex subunit MTA3 in cortical neurogenesis similar to that reported of other NuRD subunits, in which depletion during neurogenic stages leads to premature differentiation or impaired migration. Furthermore, I applied a genome-wide approach, in which I analyzed the transcriptome of different telencephalic regions, developmental time points and cell types in the murine embryonic brain, to identify key fate determinants of neurogenesis. I found that chromatin remodelers likely play a role in maintaining plasticity, and maintenance of neurogenesis is determined by region-specific gene expression. In evaluating the piggyBac transposon system for genomic integration of expression constructs in mouse neurogenic stem cells in vivo, I uncovered a phenotype of progenitor cell ectopia and cortical folding, reminiscent of basal progenitor amplification in gyrencephalic species, which is likely elicited by transposition itself. Finally, I evaluated the concurrent activation of several neurogenic determinant candidates into early gliogenic stages, and found a possible effect of prolonging neocortical neurogenesis by the simultaneous activation of 15 genes, in which the proportion of cells in the ventricular zone, as well as their expression of stem cell and progenitor markers, were increased.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Graduate School of Systemic Neurosciences (GSN)
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 8. September 2021
• 1. Bericht­erstatter:in: Götz, Magdalena