title: Notch signaling promotes nephrogenesis by downregulating Six2.
abstract: During nephrogenesis, multipotent mesenchymal nephron progenitors develop into distinct epithelial segments. Each nephron segment has distinct cell types and physiological function. In the current model of kidney development, Notch signaling promotes the formation of proximal tubules and represses the formation of distal tubules. Here, we present a novel role of Notch in nephrogenesis. We show in mice that differentiation of nephron progenitors requires downregulation of Six2, a transcription factor required for progenitor maintenance, and that Notch signaling is necessary and sufficient for Six2 downregulation. Furthermore, we find that nephron progenitors lacking Notch signaling fail to differentiate into any nephron segments, not just proximal tubules. Our results demonstrate how cell fates of progenitors are regulated by a transcription factor governing progenitor status and by a differentiation signal in nephrogenesis.
authors.affiliation: Division of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Eunah
authors.initials: E
authors.lastname: Chung
authors.affiliation: Division of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Deacon
authors.affiliation: Division of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Sierra
authors.initials: S
authors.lastname: Marable
authors.affiliation: Division of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Shin
authors.affiliation: Division of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA joo-seop.park@cchmc.org.
authors.forename: Joo-Seop
authors.identifier: 0000-0002-4190-4386
authors.initials: JS
authors.lastname: Park
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009399:Nephrons / Q000196:embryology*; D038081:Organogenesis / Q000235:genetics*; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D051880:Receptors, Notch; C497420:Six2 protein, mouse; D014157:Transcription Factors
keywords: Kidney; Mouse; Nephrogenesis; Nephron progenitors; Nephron segmentation; Notch; Six2