EXPRESSION OF GRB7 GROWTH-FACTOR RECEPTOR SIGNALING PROTEIN IN KIDNEYDEVELOPMENT AND IN ADULT KIDNEY

Grb7, a signaling protein whose physiological function is unknown, bin ds receptor tyrosine kinases important for normal kidney development. By investigating and correlating Grb7 gene expression with that report ed for Grb7-binding receptors, we provide clues to Grb7 function(s). R T-PCR and immunoblot were used to demonstrate Grb7 gene and protein ex pression in the mature kidney. Additional RT-PCR studies detected gene expression in all microdissected adult nephron segments examined, exc ept glomeruli, and in the mouse metanephric kidney from embryonic day 11 (Ell) through to day 17(E17). In situ hybridization at E14 demonstr ated the following cellular pattern of localization: Grb7 mRNA in meta nephric epithelia of mesenchymal and ureteric bud origin; no expressio n in the undifferentiated mesenchyme; and little expression in podocyt e-destined cells or primitive glomeruli. Grb7 mRNA was also present in the epithelia of the lung and gut at E14. Thus Grb7 may have a basic function in growth factor signaling in terminally differentiated epith elia along the nephron and in developing epithelia in the kidney, lung , and gut. It is localized in a pattern permissive for a role in Her2 and Ret receptor signaling.