Deletion of Notch signaling in the developing mouse kidney results in a disruption of planar cell polarity in tubule epithelial cells

Abstract

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/kCD mice to the membrane‐targeted Tomato/Green Fluorescent Protein (mT/mG) double fluorescent reporter mouse strain (Gt(ROSA)26Sortm4(ACTB‐tdTomato,‐EGFP)Luo/J), which carries a loxP‐flanked Tomato cassette. Newborn RBPJ/kCD mice exhibited medullary and cortical cystic like dilatations. Postnatal day 14 (P14), RBPJ/kCD 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/kCD 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 InformationNational Institutes of Health