Date of Award
Master of Science
As cerebellar granule neurons (CGNs) mature they undergo a specific pattern of events. However, the manner which neurons exit the germinal zone (GZ) is not entirely understood. As CGNs polarize and differentiate, they migrate from the outer to the internal layers, a process regulated by polarity genes and post-translational modifications. Due to its role in neuronal migration, we were interested in the functionof the polarity gene Pard6 and its domains. Using the structure function assays, we found that some domains were required for GZ exit. Also, a two-hybrid screen indicated that the E3 ubuiqtin ligase FbxW5 binds to the PDZ domain of Pard6. Thus, overexpression of FbxW5 resulted in an inhibited migration of CGNs, while overexpression of Pard6 restored migration. Therefore, we propose that not all domains are required for Pard6 activity in neuronal migration and there is a functional interaction between Pard6 and FbxW5 regulating cells exiting the GZ.
dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Howell, Danielle E., "Partitioning Defective Protein 6: A Mechanistic Regulator of Neuronal Migration" (2016). Electronic Theses and Dissertations. 1355.