PhD, University of Cincinnati, 2006, Medicine : Molecular and Developmental Biology

Renal morphogenesis involves the reciprocal inductive interactions between the ureteric bud and metanephric mesenchyme forming the collecting ducts and nephrons within adult kidney. We applied microarray technology to the study of renal morphogenesis in order to better understand the molecular mechanisms underlying development. Additionally, the techniques employed in the expression analysis of the embryonic kidney were extended to the study of renal disease. Embryonic kidneys representing different stages of renal development were analyzed using expression microarrays. Renal developmental analysis revealed many novel genes and genetic pathways involved in renal development. In addition, the normal renal development data provides a baseline for the analysis of gene targeted mice possessing disruptions in renal morphogenesis. Microarray analysis was also performed on the Hoxa11/Hoxd11 compound null renal defect throughout renal development. In conclusion, these microarray studies greatly advance our knowledge of gene expression within the normal renal morphogenesis and identify possible downstream candidate genes regulated by the Hox11 genes. Wnt signaling is crucial for normal renal morphogenesis. In Drosophila, the pygopus gene encodes a transcriptional co-activator required for canonical Wnt signaling. The targeted deletion of the mammalian orthologs of pygopus, Pygo1 and Pygo2, in mice was investigated in renal development. A disruption in ureteric number tip and morphology was identified in Pygo1/Pygo2 compound null kidneys. Additionally, canonical Wnt signaling as measure by the Bat-gal transgene is reduced within the ureteric compartment in Pygo1/Pygo2 null kidneys. Overall, these experiments suggest that Pygo function is required for activation of canonical Wnt signaling in the ureteric compartment of the developing kidney. Focal segmental glomerulosclerosis (FSGS) is characterized by the segmental scarring of the glomerulus, ultimately resulting loss of neph (open full item for complete abstract)

Committee: Dr. S. Potter (Advisor) Subjects: