Characterization of the CNS-specific F-box protein FBXO41 in cerebellar development

von Anna Holubowska
Dissertation
Datum der mündl. Prüfung:2013-10-23
Erschienen:2014-05-28
Betreuer:Dr. Judith Stegmüller
Gutachter:Dr. Judith Stegmüller
Gutachter:Prof. Dr. Dr. Hannelore Ehrenreich
Gutachter:Prof. Dr. André Fischer
Gutachter:Prof. Dr. Anastassia Stoykova
Gutachter:Prof. Dr. Andreas Wodarz
Gutachter:Prof. Dr. Ralf Heinrich
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-4526

 

 

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Zusammenfassung

Englisch

During neurodevelopment, processes like neurogenesis, neuronal migration and morphogenesis, as well as synaptogenesis determine the shape and function of the brain. All developmental events are highly coordinated by extrinsic and intrinsic signaling pathways. The ubiquitin-proteasome system emerges as specific intrinsic regulator of brain development as well as target for therapeutic approaches. In this study, I identified the UPS component and an F-box protein FBXO41 as a CNS-specific protein expressed exclusively in neurons. I found that FBXO41 specifically stimulates axon growth in cerebellar granule neurons in vitro and in vivo. In addition, I discovered that FBXO41 is crucial for the migration of CGNs in the developing cerebellar cortex. At the molecular level, I also found that FBXO41 fs centrosomal localization is important for its role in neuronal migration but not for axon growth. In addition, I uncovered that FBXO41 associates with DISC1 to cooperate in neuronal migration but this interaction is dispensable for axon growth regulation. Taken together, my study led to the identification of the novel CNS-specific F-box protein FBXO41 and the characterization of its role in crucial aspects of cerebellar development.
Keywords: FBXO41; neurodevelopment; axon growth; neuronal migration
 
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