title: Repair after nephron ablation reveals limitations of neonatal neonephrogenesis.
abstract: The neonatal mouse kidney retains nephron progenitor cells in a nephrogenic zone for 3 days after birth. We evaluated whether de novo nephrogenesis can be induced postnatally beyond 3 days. Given the long-term implications of nephron number for kidney health, it would be useful to enhance nephrogenesis in the neonate. We induced nephron reduction by cryoinjury with or without contralateral nephrectomy during the neonatal period or after 1 week of age. There was no detectable compensatory de novo nephrogenesis, as determined by glomerular counting and lineage tracing. Contralateral nephrectomy resulted in additional adaptive healing, with little or no fibrosis, but did not also stimulate de novo nephrogenesis. In contrast, injury initiated at 1 week of age led to healing with fibrosis. Thus, despite the presence of progenitor cells and ongoing nephron maturation in the newborn mouse kidney, de novo nephrogenesis is not inducible by acute nephron reduction. This indicates that additional nephron progenitors cannot be recruited after birth despite partial renal ablation providing a reparative stimulus and suggests that nephron number in the mouse is predetermined at birth.
authors.affiliation: Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Tögel
authors.affiliation: Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: M Todd
authors.initials: MT
authors.lastname: Valerius
authors.affiliation: Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Freedman
authors.affiliation: Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rossella
authors.initials: R
authors.lastname: Iatrino
authors.affiliation: Center for Regenerative Medicine and Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Mor
authors.initials: M
authors.lastname: Grinstein
authors.affiliation: Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage; D003452:Cryosurgery; D005355:Fibrosis; D018398:Homeodomain Proteins / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000254:growth & development / Q000473:pathology; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D009392:Nephrectomy; D009399:Nephrons / Q000254:growth & development* / Q000473:pathology; D038081:Organogenesis; D051762:PAX2 Transcription Factor / Q000378:metabolism; D013234:Stem Cells; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C497420:Six2 protein, mouse; D014157:Transcription Factors