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Deletion of Notch signaling in the developing mouse kidney results in a disruption of planar cell polarity in tubule epithelial cells
Author(s) -
Kearns Donovan,
Livingston Safia,
Baybutt Richard,
Heuvel Gregory Vanden
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1031.1
Subject(s) - notch signaling pathway , microbiology and biotechnology , biology , cell fate determination , transcription factor , notch proteins , kidney development , jag1 , signal transduction , gene , genetics , embryonic stem cell
Cux1 is the murine homologue of the Drosophila gene cut . In Drosophila, multiple genetic interactions between Cut and the Notch and Wingless signaling pathways occur during development. Cux1 is upregulated by Notch1 activation in rat kidney epithelial cells, and interacts with the groucho homologue Grg4 to regulate p27 expression in the developing kidney. To further evaluate the regulation of Cux1 by Notch signaling, we conditionally deleted RBPJ/k , a transcription factor required for canonical Notch signaling, in the developing ureteric bud and collecting duct using Cre‐recombinase (Cre) under the direction of the Hoxb7 promoter. We confirmed the Cre activity by crossing the RBPJ/k CD mice to the membrane‐targeted Tomato/Green Fluorescent Protein (mT/mG) double fluorescent reporter mouse strain (Gt(ROSA)26Sor tm4(ACTB‐tdTomato,‐EGFP)Luo /J), which carries a loxP‐flanked Tomato cassette. Newborn RBPJ/k CD mice exhibited medullary and cortical cystic like dilatations. Postnatal day 14 (P14), RBPJ/k CD mice exhibited hydronephrosis and cortical dilatations. Analysis of planar cell polarity using anti‐phospho‐Histone H3 antibodies showed a disruption of spindle orientation in the collecting ducts of RBPJ/k CD mice. Taken together, these results suggest that Notch signaling is required for the normal development of the collecting duct system in the kidney, and that reduced Notch signaling may contribute to the development of renal cysts. Support or Funding Information National Institutes of Health