Coexpression of Cux-1 and Notch signaling pathway components during kidney development.

Cux-1 is the murine homologue of the Drosophila gene cut, which is required for cellular differentiation in several tissues, including the wing margin and Malpighian tubule. Mammalian cut proteins function as cell cycle-dependent transcriptional repressors in proliferating cells. Targets of Cux-1 repression include the cyclin kinase inhibitors p21 and p27. However, little is known about the regulation of Cux-1. In Drosophila, multiple genetic interactions between Cut and the Notch and Wingless signaling pathways occur during wing development. To begin to determine whether Cux-1 regulation by the Notch signaling pathway is conserved in mammals, we compared the expression patterns of Cux-1, the murine Notch receptors (Notch 1-4), and the murine ligands (Jagged 1, Jagged 2, and Delta 1) during murine embryogenesis and kidney development. In this report, we demonstrate that Cux-1 expression overlaps with that of Notch signaling pathway components in multiple tissues during embryonic development. In the developing kidney, Cux-1 expression overlaps with that of Notch pathway components in the condensing mesenchyme, in pretubular aggregates (comma and S-shaped bodies), and in the presumptive podocytes of capillary loop stage glomeruli. Furthermore, Cux-1 was significantly up-regulated in the rat kidney epithelial cell line RKE expressing a constitutively active Notch 1, and this finding was associated with a reduction of p27. Moreover, Cux-1 interacts with the Groucho homolog TLE-4, a corepressor recruited by Notch effector proteins. Taken together, these results suggest that Cux-1 may function in the context of the Notch signaling pathway in multiple tissues during mammalian embryogenesis.