title: Proper Notch activity is necessary for the establishment of proximal cells and differentiation of intermediate, distal, and connecting tubule in Xenopus pronephros development.
abstract: BACKGROUND
  Notch signaling in pronephros development has been shown to regulate establishment of glomus and proximal tubule, but how Notch signal works on competency of pronephric anlagen during the generation of pronephric components remains to be understood.
  
  
  RESULTS
  We investigated how components of pronephros (glomus, proximal tubule, intermediate tubule, distal tubule, and connecting tubule) were generated in Xenopus embryos by timed overactivation and suppression of Notch signaling. Notch activation resulted in expansion of the glomus and disruption of the proximal tubule formation. Inhibition of Notch signaling reduced expression of wt1 and XSMP-30. In addition, when Notch signaling was overactivated at stage 20 on, intermediate, distal, and connecting tubule markers, gremlin and clcnkb, were decreased while Notch down-regulation increased gremlin and clcnkb. Similar changes were observed with segmental markers, cldn19, cldn14, and rhcg on activation or inhibition of Notch. Although Notch did not affect the expression of pan-pronephric progenitor marker, pax2, its activation inhibited lumen formation in the pronephros.
  
  
  CONCLUSIONS
  Notch signal is essential for glomus and proximal tubule development and inhibition of Notch is critical for the differentiation of the intermediate, distal, and connecting tubule.
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Katada
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000196:embryology*; D060910:Pronephros / Q000166:cytology / Q000196:embryology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D000943:Antigens, Differentiation; C549535:NOTCH1 protein, Xenopus; D051880:Receptors, Notch
keywords: Notch; Xenopus laevis; pronephros