EXPRESSION OF RET 3'-SPLICING VARIANTS DURING HUMAN KIDNEY DEVELOPMENT

The mature mammalian kidney arises through a series of reciprocal indu ctive interactions between two different cell groups, the ureteric bud epithelium and the metanephric mesenchyme, The RET receptor tyrosine kinase is required for induction and development of the metanephric ki dney. Differential splicing at the 3' end of RET results in transcript s encoding three isoforms that differ with respect to their C-terminal 9 (RET9), 51 (RET51) or 43 (RET43) amino acids, In vitro assays have identified differences in the abilities of the RET9 and RET51 isoforms to induce differentiation suggesting functional differences between t hese proteins. We examined the relative expression levels of the three RET 3' splicing variants in developing human kidney using semi-quanti tative RT-PCR. We observed consistent expression of the RET9 and RET43 variants in kidney samples spanning 7.5 through 24 weeks gestation, A t early gestational ages (7.5-8.5 weeks), RET51 expression was very lo w (+/-5%) compared to RET9; however, a rapid seven fold increase in ex pression was detected by 9 weeks. Our data suggest that RET51 may cont ribute to differentiation-related events occurring after 8.5 weeks ges tation rather than to induction of the human kidney.