Defining the role of SOX4/SOX11 during nephrogenesis In Vivo
King, Morgan Leslie
Honours
2018
Hartwig, Sunny
Faculty of Arts. Island Studies.
Biology
Biomedical Sciences
University of Prince Edward Island
Charlottetown, PE
Congenital anomalies of the kidney and urinary tract (CAKUT) account for the highest incidence of end-stage renal disease in children. To understand abnormalities in renal development, a greater understanding of nephrogenesis is necessary. SOX genes have been identified to be critical in a number of organogenesis processes, but they have not been extensively studied in the kidney. Previous research has characterized Sox4's importance in the formation of nephrons - conditional ablation of Sox4 Show moreCongenital anomalies of the kidney and urinary tract (CAKUT) account for the highest incidence of end-stage renal disease in children. To understand abnormalities in renal development, a greater understanding of nephrogenesis is necessary. SOX genes have been identified to be critical in a number of organogenesis processes, but they have not been extensively studied in the kidney. Previous research has characterized Sox4's importance in the formation of nephrons - conditional ablation of Sox4 resulted in end-stage renal failure. In a complementary study, it was determined that Sox4!11 double knock-out mice die perinatally of renal failure. Analysis revealed a high number of immature nephrons. It was hypothesized that SOX4 and SOXJ 1 cooperatively promote differentiation during renal organogenesis in vivo. Furthermore, it was predicted that the etiology ofrenal failure/death in Sox4/J J double knock-out mice was due to a primary delay in nephron differentiation, leading to perinatal renal incompetence and subsequent death. To test the hypothesis, a morphometric approach was adopted. Nephrons were quantified in kidney sections using a virtual disector method in 5 different genotypes: Sox4+/Soxl r , Sox4HZ/Sox] JHZ, Sox4HZ/SoxJ JK0 , Sox4K0 JSoxJ JHZ, and Sox4K0 JSoxJ JK0 . Mature glomeruli were quantified at embryonic day (E) 18. 5 and postnatal day 21 using a combination of peanut agglutinin staining and haematoxylin & eosin staining. Mature glomeruli were also quantified at El4.5, El 6.5 , and El 8.5 using WTI immunofluorescence to assess whether there was a primary delay in nephron development. Results demonstrate that SOX4 and SOXJ 1 have important independent roles, but cooperative signaling is required for normal renal development in vivo. Show less
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