Date of Completion
Mutation of Citron-Kinase (Cit-K) in rodents causes substantial reductions in the number of neurons generated in the CNS and results in a primary microcephaly-like phenotype. Evidence from drosophila genetics has further established a genetic link between Cit-K and a protein Argonaut 1 (AGO1), which is required for proper functioning of the miRNA machinery (2). Experiments characterizing the role of miRNAs in the developing cortex demonstrate the requirement of miRNAs for differentiation of neural progenitor cells starting at embryonic day 12.5 (3). Together, this evidence links the role of miRNAs to neurogenesis and thus this relationship warrants further investigation. Here miRNA expression has been characterized between the wild type (wt) and the Cit-K mutant rat (Cit-Kfh/fh). Two bioinformatics approaches were utilized to analyze transcriptome analysis data comparing expression between the wt and Cit-Kfh/fh. Evaluation of miRNA expression between neural progenitor cells (NPCs) and cells grown in mitogen free media with BDNF+ (MFBCs) revealed diminished miRNA expression in Cit-Kfh/fh NPCs upon removal of mitogens and addition of BDNF. Lastly, miRNA target prediction software was used to tabulate all highly predicted and verified gene targets for comparison with transcriptome analysis data. Gene targets of the down-regulated miRNAs in the MFBC population correlated with an up-regulation of those respective transcript levels in the transcriptome analysis dataset. These results confirm the possibility that miRNAs play a role in mediating the changes in transcript levels that appear upon the loss of Cit-K.
Parikh, Shan, "Investigation of miRNAs Expression in a Citron-Kinase Mutant Model of Microcephaly" (2011). Master's Theses. Paper 99.