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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25811

Title: Activated HH Signaling: Deleterious Lineage-dependent Effects on Nephrogenesis and Collecting Duct Formation
Authors: Staite, Marian Vicky
Advisor: Rosenblum, Norman D.
Department: Physiology
Keywords: Kidney, Hedgehog, Patched, Mesenchyme, UPJ, Gli, HH, Nephrogenesis
Issue Date: 11-Jan-2011
Abstract: Hedgehog (HH) signaling controls renal development. Mutations in PTC1, the HH receptor, cause cancer in non-renal tissues. We hypothesized that constitutively active HH signaling is deleterious to renal development in mice with PTC1 deficiency targeted to the metanephric mesenchyme (MM)(Rarb2-Cre;Ptc1 loxP/-, termed Ptc1 mutants). Increased HH signaling in MM of mutant mice was confirmed by qRT-PCR for Ptc1. A decrease in NCAM-positive nephrogenic precursors at E13.5 and WT1-positive glomeruli at E18.5 was found. Increased cortical expression of Foxd1 was observed. At E13.5, a cluster of ectopic cells expressing Raldh2, Ptc2 and Bmp4 accumulated at the presumptive uretero-pelvic junction (UPJ). Magnetic resonance imaging demonstrated an increase in pelvic volume. Constitutive expression of GLI3 repressor via the Gli3Δ699 allele in Ptc1 mutants increased nephron number comparable to wild type mice and decreased pelvic volume compared to Ptc1 mutants. Thus repression of HH activity is required for proper nephrogenesis and patterning of the UPJ.
URI: http://hdl.handle.net/1807/25811
Appears in Collections:Master

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