Loss of BAF155 impairs neurogenesis in the developing olfactory system of mice
von Christina Bachmann
Datum der mündl. Prüfung:2019-12-09
Erschienen:2019-11-19
Betreuer:Prof. Dr. Jochen Staiger
Gutachter:Prof. Dr. Jörg Großhans
Gutachter:Prof. Dr. Rainer Mausberg
Dateien
Name:letztendliche_Diss_2.pdf
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Zusammenfassung
Englisch
Neurogenesis is a core developmental process which comprises the maturation of neural stem cells to fully developed neurons. Former studies have provided evidence that in the neuronal development of the central nervous system, chromatin remodeling mSWI/SNF (BAF) complexes are indispensable factors to guide the proliferation and renewal of cells. Accordingly, given the key role in the central nervous system, the BAF complex currently receives scientific attention in how it regulates neurogenesis. As the olfactory epithelium constitutes an exceptional tissue, characterized by self-renewing capacities throughout life, it serves as an excellent model to ex-plore how neurogenesis is controlled at cellular and molecular levels (Kawauchi 2005). Thus, this study sheds light on the role of the scaffolding subunit BAF155 in the development of the olfactory system of mice. It must be highlighted that BAF155 is ubiquitously expressed in the neuronal and non-neuronal cell lineages of the olfactory epithelium. On the basis of this finding, I analyzed the phenotype of a BAF155 conditional knockout mutant by means of immunohistochemical tracings in the olfactory epithelium of mice. The BAF155cKO phenotype is characterized by a macroscopic loss of the olfac-tory bulb despite inductional signals in the corresponding region of the fore-brain, an impaired proliferation of the oNSC population and a defect in the mat-uration of ORNs which results in a thinner OE and as well in a loss of axonal projections to higher brain regions. However, BAF155 is no universal modulator of olfactory cellular proliferation, as the population of glial-like sustentacular cells is totally preserved in the BAF155cKO mutant. Furthermore, the early neu-ronal specification around E10.5 from oNSC to immature ORN seems to be preserved. Further studies may be acquired in order to complete our comprehension of the processing of oNSCs into sustentacular cells and why this developmental path-way is not affected by a loss of BAF155. Closer investigations should also be invested in sorting out, whether the development of the olfactory bulb is condi-tional upon physiologic axonal connections between OE and OB.
Keywords: BAF155; mSWI/SNF(BAF)complexes
Schlagwörter: BAF155; mSWI/SNF(BAF)complexes