THE EXPRESSION OF RET AND ITS MULTIPLE SPLICE FORMS IN DEVELOPING HUMAN KIDNEY

A series of inductive events between two different cell groups, the ur eteric bud epithelium and metanephric mesenchyme, gives rise to the fu nctional mammalian kidney, These reciprocal inductive interactions inv olve a number of molecules, one of which is the RET receptor tyrosine kinase, The phenotype of mice lacking functional RET includes kidney a genesis or severe dysgenesis, indicating a requirement for RET in kidn ey organogenesis, To investigate RET expression in human kidney develo pment, we used a semi-quantitative RT-PCR-based strategy to examine a panel of kidney RNA samples ranging from 8-24 weeks gestational age, W e found RET expression was highest earlier in development (14 weeks) w ith expression decreasing through to 24 weeks gestation, While three a lternative RET transcripts generated by exon skipping at the 5' end of the gene were all detected throughout kidney development, expression of one transcript, RET2/6, where exon 2 was spliced to exon 6, varied relative to full length RET during this period, Levels of RET2/6 were highest at the earliest age of fetal kidney examined (8 weeks) and dec reased relative to all other RET transcripts to low adult levels, The period of high expression coincides with a period of rapid bud bifurca tion, Thus, it is possible that RET2/6 has a role in the early growth and differentiation of the human kidney.