title: Coexpression of Cux-1 and Notch signaling pathway components during kidney development.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Sharma
authors.forename: Amber
authors.initials: A
authors.lastname: Fopma
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Brantley
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Vanden Heuvel
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D007668:Kidney / Q000196:embryology* / Q000502:physiology*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; C000624101:Cux1 protein, mouse; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; C000606275:Jag1 protein, rat; C490503:Jag2 protein, mouse; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008024:Ligands; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; C084532:Tle4 protein, rat; C064045:delta protein