title: Role of CD34 family members in lumen formation in the developing kidney.
abstract: Previous studies have shown CD34 family member Podocalyxin is required for epithelial lumen formation in vitro. We demonstrate that Endoglycan, a CD34 family member with homology to Podocalyxin, is produced prior to lumen formation in developing nephrons. Endoglycan localizes to Rab11-containing vesicles in nephron progenitors, and then relocalizes to the apical surface as progenitors epithelialize. Once an apical/luminal surface is formed, Endoglycan (and the actin-binding protein Ezrin) localize to large, intraluminal structures that may be vesicles/exosomes. We generated mice lacking Endoglycan and found mutants had timely initiation of lumen formation and continuous lumens, similar to controls. Mice with conditional deletion of both Endoglycan and Podocalyxin in developing nephrons also had normal tubular lumens. Despite this, Endoglycan/Podocalyxin is required for apical recruitment of the adaptor protein NHERF1, but not Ezrin, in podocyte precursors, a subset of the epithelia. In summary, while CD34 family members appear dispensable for lumen formation, our data identify Endoglycan as a novel pre-luminal marker and suggest lumen formation occurs via vesicular trafficking of apical cargo that includes Endoglycan.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zhufeng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Zimmerman
authors.affiliation: Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Tsunezumi
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Braitsch
authors.affiliation: Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Cary
authors.initials: C
authors.lastname: Trent
authors.affiliation: Cancer Research UK (CRUK) Beatson Institute, and Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Bryant
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ondine
authors.initials: O
authors.lastname: Cleaver
authors.affiliation: Centre of Biological Research, CIB-CSIC, Madrid, Spain; CIBER of Rare Diseases, ISCIII, Madrid, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: González-Manchón
authors.affiliation: Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: denise.marciano@utsouthwestern.edu.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Marciano
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D009399:Nephrons / Q000196:embryology* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D050199:Podocytes / Q000166:cytology; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000099149:Ezrin
chemical_list: D018952:Antigens, CD34; D003598:Cytoskeletal Proteins; D009077:Mucins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin; C406902:endoglycan; C001643:podocalyxin; C093376:sodium-hydrogen exchanger regulatory factor
keywords: CD34; Endoglycan; Kidney development; Lumen; Nephron; Podocalyxin; Polarity; Tubulogenesis