| dc.contributor.advisor | Staiger, Jochen F. Prof. Dr. | |
| dc.contributor.author | Kiszka, Kamila Anna | |
| dc.date.accessioned | 2019-12-20T11:01:52Z | |
| dc.date.available | 2019-12-20T11:01:52Z | |
| dc.date.issued | 2019-12-20 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0005-12DE-D | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7790 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7790 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | A guardian of balance: the role of BAF chromatin remodeling complex in astrogliogenesis during mouse forebrain development | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Staiger, Jochen F. Prof. Dr. | |
| dc.date.examination | 2019-05-15 | |
| dc.description.abstracteng | In the human central nervous system, astrocytes vastly outnumber neurons and regulate a host of
physiological processes critical to its function. Astrocytes form a functional syncytium tiling the brain
with minimal overlap between individual cells. This anatomical organization implies that a balanced
numbers of neurons and astrocytes must be generated during brain development. In spite of this,
very little is known about the molecular events governing proliferation and differentiation in the
astroglial lineage that culminate in the establishment of adequate numbers of astrocytes.
In recent years, the chromatin remodeling BAF (Brg1/Brm Associated Factors) complex, a
conglomerate of at least 15 protein subunits, has emerged as a key regulator of different steps of
neurogenesis, from proliferation of progenitors to differentiation into mature neurons, thus
profoundly affecting brain development. However, its functions in astrogliogenesis are largely
unknown.
Here, we investigated the involvement of BAF complex in the regulation of cellular proliferation and
differentiation in the astroglial lineage of perinatal mouse brain.
We first assessed the expression of several BAF complex subunits in cells of both neuronal and
astroglial lineages, and found that the composition of the BAF complex was cell type dependent.
Next, we examined the phenotype of a mouse model in which hGFAP-Cre driven conditional
knockout of BAF155 and BAF170, two scaffolding subunits, results in the deletion of the entire BAF
complex within radial glial progenitors during late neurogenesis and astrogliogenesis. Performing
phenotype and gene expression profile analyzes, we found that loss of BAF complex at this
developmental stage causes a tremendous depletion of neuronal cells as well as an aberrantly
increased abundance of proliferative astroglia in ventral and dorsal telencephalon. Furthermore, we
identified an upregulated expression of GLI1 as a causal mechanism of abnormal overproliferation of
astroglial cells following BAF complex depletion. This could be demonstrated by inhibition of GLI1 by
injection of GANT61, which abolished the aberrant proliferation caused by loss of BAF complex.
We thus propose that cell lineage dependent rearrangements of the composition of the BAF
complex play a crucial role in regulating the relative numbers of neurons and astrocytes generated
during brain development. This effect is achieved in part by BAF complex dependent repression of
the proliferation-enhancing mitogen GLI1 in the astroglial lineage. | de |
| dc.contributor.coReferee | Dresbach, Thomas Prof. Dr. | |
| dc.subject.eng | BAF complex, astrogliogenesis, mouse development | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-12DE-D-5 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 1686307543 | |