| dc.contributor.advisor | Henningfeld, Kristine Dr. | |
| dc.contributor.author | Berndt, Rolf Patrick | |
| dc.date.accessioned | 2016-06-23T08:19:38Z | |
| dc.date.available | 2016-06-23T08:19:38Z | |
| dc.date.issued | 2016-06-23 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0028-8793-8 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5704 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Functional analysis of Prdm14 during Xenopus embryogenesis | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Bucher, Gregor Prof. Dr. | |
| dc.date.examination | 2015-06-29 | |
| dc.description.abstracteng | Prdm14 is a member of the conserved family of Prdm proteins, which are
emerging as crucial regulators of multiple early developmental processes and
diseases. Members of the Prdm family are characterized by the presence of a
single PR domain and a variable number of DNA-binding zinc fingers. Most
members of the Prdm proteins directly influence transcription through intrinsic
histone methyltransferase activity or recruitment of cofactors. In this thesis, a
functional analysis of Prdm14 was undertaken to elucidate its role during early
vertebrate development using the X. laevis model system.
Prdm14 is expressed during gastrulation in the prospective
neuroectoderm. At late neural plate stages, the expression is restricted to the
territories of primary neurogenesis. In tailbud stage embryos, expression of
prdm14 is detected in postmitotic neurons of the central nervous system and a
subset of the cranial ganglia. Prdm14 is regulated positively by the proneural
bHLH gene neurog2 and negatively by the Notch signaling pathway, which is
strongly suggestive for a role during primary neurogenesis. Overexpression of
prdm14 in X. laevis embryos promotes the proliferation of neural progenitor
cells, which results in the expansion of the neural plate and in a transient
inhibition of neuronal differentiation. In tailbud stage embryos, prdm14
overexpression induces the formation of ectopic neurons in the non-neural
ectoderm that express markers indicative of a sensory glutamatergic neuronal
cell fate. In pluripotent animal cap cells, prdm14 overexpression is sufficient to
induce a glutamatergic neuronal cell fate supporting the studies in embryos.
The downstream transcriptional network induced by prdm14 was studied
through RNA-sequencing analysis of prdm14-injected animal caps at the
equivalent of neural plate and tailbud stage. Predominant among the prdm14-
upregulated genes were ligands and signaling components of the Wnt pathway
and Wnt-regulated genes. Consistent with the RNA-sequencing analysis,
prdm14 overexpression in the embryo activated a canonical Wnt-signaling
reporter. In addition, many of the upregulated genes have previously been
shown to be involved in neural crest and sensory neuron specification, including
the key neural plate border specifiers pax3 and zic1. The activation of these
genes may in part be attributed to the ability of prdm14 to activate canonical Wnt-signaling. Taken together, the results of this thesis provide evidence for
multiple roles of Prdm14 during the development of the nervous system. During
gastrulation Prdm14 promotes maintenance of the neural ectoderm and the
specification of the neural plate border, which will give rise to neural crest and
Rohon-Beard sensory neurons. Also suggested by the expression and
regulation of prdm14, is a role during neuronal differentiation and maturation. | de |
| dc.contributor.coReferee | Wodarz, Andreas Prof. Dr. | |
| dc.subject.eng | Xenopus | de |
| dc.subject.eng | Prdm14 | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0028-8793-8-9 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 861891635 | |