EXPRESSION OF A CUT-RELATED HOMEOBOX GENE IN DEVELOPING AND POLYCYSTIC MOUSE KIDNEY

cut is a diverged homeobox gene that is essential for normal developme nt of the Malpighian tubules in Drosophila melanogaster. Homologues of Drosophila cut that encode transcriptional repressors have been ident ified in several mammalian species and cell lineages. We examined the expression of a murine cut homologue (named Cux-1) in the developing m ouse using Northern blot analysis and in situ hybridization. At 12.5 d .p.c. and 13.5 d.p.c., Cux-1 was highly expressed in a subset of embry onic tissues, including the developing metanephros. Within the metanep hros, Cux-1 was expressed in the nephrogenic zone including both mesen chymal cells (uninduced and condensed mesenchyme) and epithelial cells (ureteric buds, renal vesicles, S-shaped bodies). During later stages of nephrogenesis, Cux-1 was down-regulated such that there was minima l expression in mature glomeruli and tubules. In addition, Cux-1 was d etected in the mesonephros, mesonephric duct, and bladder. Expression of Cux-1 was also examined in polycystic kidneys from C57BL/6J-cpk/cpk mice. At 21 days of age, Cux-1 was highly expressed in cyst epitheliu m of polycystic kidneys but was minimally expressed in kidneys from ph enotypically normal littermates. These results demonstrate that a cut- related homeobox gene is expressed in the developing kidney and urinar y tract of the mouse. Expression of Cux-1 in the kidney is inversely r elated to degree of cellular differentiation. Cux-1 may encode a trans criptional repressor that inhibits terminally differentiated gene expr ession during early stages of nephrogenesis.