Date of Degree
2010
Document Type
dissertation
Degree Name
PhD (Doctor of Philosophy)
Department
Molecular Physiology and Biophysics
First Advisor
Beverly L. Davidson
Abstract
MicroRNA (miRNA) function is required for normal animal development, in particular in stem cell and precursor populations. I hypothesize that miRNAs are similarly required for stem cell maintenance and appropriate fate commitment in the brain. To test the requirement for global microRNA production, I depleted the microRNA biosynthetic enzyme DICER in the developing mouse brain. I found that DICER loss in embryonic neural progenitor cells leads to embryonic lethality with microcephaly. By histological analysis, I found defects in both neural progenitor cell maintenance and cell differentiation. I also identified new candidate microRNAs for this phenotype by profiling miRNAs in DICER-depleted and control cells. Three microRNAs which are good candidates to modulate nervous differentiation are miR-23b, -182, and -34a. I describe the expression pattern and functional characterization of these candidates. In particular, miR-34a depletes neuron production after progenitor cell differentiation in culture, likely by modulating cell cycling and Notch pathway genes.
Pages
xii, 141
Bibliography
130-141
Copyright
Copyright 2010 Sarah Kathryn Fineberg
Recommended Citation
Fineberg, Sarah Kathryn. "MicroRNAs' role in brain development and disease." dissertation, University of Iowa, 2010.
http://ir.uiowa.edu/etd/498.