title: Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment.
abstract: While nephron formation is known to be initiated by a mesenchyme-to-epithelial transition of the cap mesenchyme to form a renal vesicle (RV), the subsequent patterning of the nephron and fusion with the ureteric component of the kidney to form a patent contiguous uriniferous tubule has not been fully characterized. Using dual section in situ hybridization (SISH)/immunohistochemistry (IHC) we have revealed distinct distal/proximal patterning of Notch, BMP and Wnt pathway components within the RV stage nephron. Quantitation of mitoses and Cyclin D1 expression indicated that cell proliferation was higher in the distal RV, reflecting the differential developmental programs of the proximal and distal populations. A small number of RV genes were also expressed in the early connecting segment of the nephron. Dual ISH/IHC combined with serial section immunofluorescence and 3D reconstruction revealed that fusion occurs between the late RV and adjacent ureteric tip via a process that involves loss of the intervening ureteric epithelial basement membrane and insertion of cells expressing RV markers into the ureteric tip. Using Six2-eGFPCre x R26R-lacZ mice, we demonstrate that these cells are derived from the cap mesenchyme and not the ureteric epithelium. Hence, both nephron patterning and patency are evident at the late renal vesicle stage.
authors.affiliation: NHMRC Principal Research Fellow, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.
authors.forename: Kylie
authors.initials: K
authors.lastname: Georgas
authors.forename: Bree
authors.initials: B
authors.lastname: Rumballe
authors.forename: M Todd
authors.initials: MT
authors.lastname: Valerius
authors.forename: Han Sheng
authors.initials: HS
authors.lastname: Chiu
authors.forename: Rathi D
authors.initials: RD
authors.lastname: Thiagarajan
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lesieur
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Eric W
authors.initials: EW
authors.lastname: Brunskill
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Combes
authors.forename: Dave
authors.initials: D
authors.lastname: Tang
authors.forename: Darrin
authors.initials: D
authors.lastname: Taylor
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.forename: S Steven
authors.initials: SS
authors.lastname: Potter
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Little
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D064026:Calbindins; D049109:Cell Proliferation; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000502:physiology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000033:anatomy & histology* / Q000196:embryology* / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009399:Nephrons / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014513:Ureter / Q000033:anatomy & histology / Q000196:embryology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D015820:Cadherins; D064026:Calbindins; D024141:Collagen Type IV; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D007797:Laminin; C499523:Lhx1 protein, mouse; D051880:Receptors, Notch; D064030:S100 Calcium Binding Protein G; D014157:Transcription Factors; D051153:Wnt Proteins