Kalchhauser, Irene. Regulation of the self-renewal vs. differentiation decision in the C.elegans germline. 2011, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9561
C.elegans germline stem cells, which are maintained by Notch signaling, constitute an excellent model to study the regulation of stem cell identity. C.elegans is amenable to genetic manipulation, to gene knockdown by RNAi, and to transgenesis. Additionally, the C.elegans germline can be readily monitored in live animals through the transparent cuticle as well as dissected for gene expression studies or immunofluorescence.
Here, we use these tools to identify genes that respond to Notch signaling in germline stem cells. We find that many Notch responsive genes reside on the X chromosome. In the following, we uncover a crosstalk between Notch signaling and the C.elegans Polycomb proteins MES-2,-3,-4, and -6, which are known to repress X linked genes in the germline.
Additionally, we identify a role of the CIP/KIP cell cycle inhibitor CKI-2 in the self-renewal versus differentiation decision of C.elegans germline stem cells. We find that CKI-2 is a key target of two conserved stem cell regulators, the RNA binding proteins FBF/Pumilio and MEX-3. Particularly FBF/Pumilio proteins have been implied in stem cell regulation in many organisms, and in C.elegans are required to maintain stem cells during adulthood. Key targets among the mRNAs targeted by FBF/Pumilio proteins have however remained elusive. We demonstrate that both MEX-3 and FBF/Pumilio proteins associate with the cki-2 3’UTR, that FBF/Pumilio binding elements are required for 3’UTR mediated regulation in vivo, and that regulation of CKI-2 by FBF/Pumilio contributes to the maintenance of germline stem cells.
|Committee Members:||Schroeder, Renee|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI|
|Bibsysno:||Link to catalogue|
|Number of Pages:||135 S.|
|Last Modified:||30 Jun 2016 10:42|
|Deposited On:||20 Sep 2011 14:56|
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