title: Role for compartmentalization in nephron progenitor differentiation.
abstract: Embryonic nephron progenitor cells are segregated in molecularly distinct compartments of unknown function. Our study reveals an integral role for bone morphogenetic protein-SMAD in promoting transition of progenitors from the primitive Cbp/p300-interacting transactivator 1 expressing (CITED1+) compartment to the uniquely sine oculis-related homeobox 2 expressing (SIX2-only) compartment where they become inducible by wingless-type mouse mammary tumor virus integration site family member (WNT)/β-catenin signaling. Significantly, CITED1(+) cells are refractory to WNT/β-catenin induction. We propose a model in which the primitive CITED1(+) compartment is refractory to induction by WNT9b/β-catenin, ensuring maintenance of undifferentiated progenitor cells for future nephrogenesis. Bone morphogenetic protein 7-SMAD is then required for transition to a distinct compartment in which cells become inducible by WNT9b/β-catenin, allowing them to progress toward epithelialization.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Brown
authors.forename: Sree Deepthi
authors.initials: SD
authors.lastname: Muthukrishnan
authors.forename: Justin A
authors.initials: JA
authors.lastname: Guay
authors.forename: Derek C
authors.initials: DC
authors.lastname: Adams
authors.forename: Dillon A
authors.initials: DA
authors.lastname: Schafer
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fetting
authors.forename: Leif
authors.initials: L
authors.lastname: Oxburgh
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D055419:Bone Morphogenetic Protein 7; C102208:Cited1 protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C497420:Six2 protein, mouse; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; C515303:Wnt9b protein, mouse; D051176:beta Catenin; C525820:bmp7 protein, mouse