Cortical patterning and neuronal migration are under the guide of BAF complex functionality

Sokpor, Godwin

dc.contributor.advisor	Staiger, Jochen Prof. Dr.
dc.contributor.author	Sokpor, Godwin
dc.date.accessioned	2020-03-26T12:17:25Z
dc.date.available	2021-11-25T00:50:04Z
dc.date.issued	2020-03-26
dc.identifier.uri	http://hdl.handle.net/21.11130/00-1735-0000-0005-136E-B
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-7927
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	Cortical patterning and neuronal migration are under the guide of BAF complex functionality	de
dc.type	cumulativeThesis	de
dc.contributor.referee	Manzini, Ivan Prof. Dr.
dc.date.examination	2019-11-27
dc.description.abstracteng	The brain is one of the complex organs designed under the control of a plethora of molecular and cellular regulatory mechanisms, including transcriptional and epigenetic pathways. Brain organogenesis proceeds in a stepwise manner involving both embryonic and postnatal cell biological processes. Such crucial processes include patterning, neurogenesis, and neuronal migration. Patterning of the brain ensures early regional subdivision of the telencephalon and functional areal sculpting of the cortex, neurogenesis is the process of neuronal production, and newly generated neurons migrate to their structural and functional maturation site in the cortex via the process of migration. The ATP-dependent chromatin remodeling BAF complex is one of the powerful epigenetic regulators of several aspects of brain development, although some of its functions thereof are only implicated and not clearly defined. How the BAF complex regulates patterning of the dorsal aspect of the telencephalon and radial glia fiber-dependent neuron migration, are the main themes of this dissertation aimed at expanding the neurodevelopmental importance of the chromatin remodelers during cortical histogenesis. By adopting a conditional genetic manipulation scheme of deleting the two BAF complex scaffolding subunits BAF155 and BAF170, we were able to generate mouse mutants that lacked the expression of BAFs in the cortex. It was observed that early patterning of the dorsal telencephalon that leads to delineation of the midline telencephalic structures such as the hem and hippocampus from the dorsolateral telencephalon (neocortex) is perturbed in the absence of BAF complex. The BAF complex-deficient dorsal telencephalon displayed an expanded hem, no hippocampal primordium, and marked medialization of the ensuing cortex. The BAF complex was identified to cooperate with the transcription and patterning factor LHX2 to drive the regional patterning of the dorsal telencephalon. Strikingly, neurons are utterly misplaced in the mis-patterned BAF complex-ablated dorsal telencephalon, raising the possibility of cortical laminar mis-patterning at later stages of forebrain development. Indeed, the late embryonic and early postnatal developing BAF complex mutant cortices are improperly laminated. Abnormal radial neuronal migration was identified to underscore the disturbed layer formation which specifically stemmed from the loss of radial glia fibers/scaffolds, depletion of cell adhesion, and sub-optimal neuronal polarization following deletion of BAF complex in neural progenitors and/or postmitotic neurons. Interestingly, the WNT signaling was shown to be modulated by the BAF complex to afford normal radial migration of cortical neurons. Altogether, these current investigations have provided insights into how the chromatin remodeling BAF complex contributes to cortical morphogenesis through regulating the regional subdivision of the dorsal telencephalon and neuronal placement during the cytoarchitectural organization of the cortex. Our current findings further clarify the multifaceted means by which the BAF complex regulates brain development and offers additional potential targets for therapeutic consideration in neurodevelopmental disorders imputable to malfunction of the BAF complex in the mammalian brain.	de
dc.contributor.coReferee	Henningfeld, Kristine Dr.
dc.contributor.thirdReferee	Dresbach, Thomas Prof. Dr.
dc.contributor.thirdReferee	Mansouri, Ahmed Prof. Dr.
dc.contributor.thirdReferee	Stoykova, Anastassia Prof. Dr.
dc.subject.eng	BAF (mSWI/SNF) complex	de
dc.subject.eng	Brain development	de
dc.subject.eng	Patterning	de
dc.subject.eng	Radial migration	de
dc.subject.eng	Chromatin remodeling	de
dc.subject.eng	Embryogenesis	de
dc.subject.eng	Radial glial fibers	de
dc.subject.eng	Cell adhesion	de
dc.subject.eng	Cortical lamination	de
dc.subject.eng	Corticogenesis	de
dc.identifier.urn	urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-136E-B-8
dc.affiliation.institute	Biologische Fakultät für Biologie und Psychologie	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2021-11-25
dc.identifier.ppn	1693388278

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1112]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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