Primary disorders of renal development account for nearly 20% of children who require treatment for end-stage renal disease. In some there is selective growth failure of renal tissue (eg. renal hypoplasia), while in others, it is the pattern of cellular growth which is deranged (eg. renal dysplasia, cystic kidneys) . In this application we propose studies of specific cell surface molecules which may regulate cell proliferation (Epidermal growth factor receptor; EGF-R) and cell attachment (E-Cadherin; E-Cad) during nephrogenesis. We will utilize monolayer and organotypic culture of human fetal kidney (HFK) to examine the developmental biology of these molecules. We will also characterize the pattern of E-Cad and EGF-R gene expression in normal and cystic kidney to determine whether a perturbation of these critical regulatory proteins might contribute to the pathogenesis of cystic kidney diseases. Specific experiments include: A) Localization of TGF-Alpha and EGF-R in human fetal kidney by In Situ hybridization and immunohistochemistry. B) Study of EGF-R regulation in cultured human fetal kidney cells and its control by Wilms' tumour gene and nerve growth factor. C) Regulation of E-Cad in HFK cells and the effect of E-Cad inhibition on HFK cell proliferation and human fetal explant morphogenesis. D) The integrity of EGF-R and E-Cad expression in autosomal dominant polycystic kidney and multicystic/dysplastic kidney. These studies are part of our long-term goal to define the cascade of molecular signals which regulate normal development of human kidney, and which, if perturbed, lead to congenital renal disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK045665-01
Application #
3247175
Study Section
General Medicine B Study Section (GMB)
Project Start
1992-09-30
Project End
1995-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mcgill University
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 0-G4
Torban, E; Pelletier, J; Goodyer, P (1997) F329L polymorphism in the human PAX8 gene. Am J Med Genet 72:186-7