Journal
DEVELOPMENTAL BIOLOGY
Volume 418, Issue 1, Pages 66-74Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2016.08.009
Keywords
Kidney development; Lumen; Tubulogenesis; Endoglycan; Podocalyxin; CD34; Polarity; Nephron
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Funding
- Basil O'Connor Starter Scholar Research Award from the March of Dimes Foundation [5-FY13-201]
- Satellite Healthcare Coplon Grant
- National Institutes of Health [R01 DK099478, P30DK079328]
- Ministerio de Economia y Cornpetitividad of Spain [FU2010-15237]
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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. (C) 2016 Elsevier Inc. All rights reserved.
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