title: The receptor tyrosine kinase regulator Sprouty1 is a target of the tumor suppressor WT1 and important for kidney development.
abstract: WT1 encodes a transcription factor involved in kidney development and tumorigenesis. Using representational difference analysis, we identified a new set of WT1 targets, including a homologue of the Drosophila receptor tyrosine kinase regulator, sprouty. Sprouty1 was up-regulated in cell lines expressing wild-type but not mutant WT1. WT1 bound to the endogenous sprouty1 promoter in vivo and directly regulated sprouty1 through an early growth response gene-1 binding site. Expression of Sprouty1 and WT1 overlapped in the developing metanephric mesenchyme, and Sprouty1, like WT1, plays a key role in the early steps of glomerulus formation. Disruption of Sprouty1 expression in embryonic kidney explants by antisense oligonucleotides reduced condensation of the metanephric mesenchyme, leading to a decreased number of glomeruli. In addition, sprouty1 was expressed in the ureteric tree and antisense-treated ureteric trees had cystic lumens. Therefore, sprouty1 represents a physiologically relevant target gene of WT1 during kidney development.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gross
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Morrison
authors.forename: Deborah P
authors.initials: DP
authors.lastname: Hyink
authors.forename: Kylie
authors.initials: K
authors.lastname: Georgas
authors.forename: Milton A
authors.initials: MA
authors.lastname: English
authors.forename: Mathias
authors.initials: M
authors.lastname: Mericskay
authors.forename: Seiyu
authors.initials: S
authors.lastname: Hosono
authors.forename: David
authors.initials: D
authors.lastname: Sassoon
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Wilson
authors.forename: Melissa
authors.initials: M
authors.lastname: Little
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Licht
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D002843:Chromatin / Q000378:metabolism; D003001:Cloning, Molecular; D004330:Drosophila; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000196:embryology; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D009841:Oligonucleotides / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D025721:WT1 Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D008565:Membrane Proteins; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; C425468:Spry1 protein, mouse; D025721:WT1 Proteins