title: Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development.
abstract: Kidney formation involves patterning events that induce renal progenitors to form nephrons with an intricate composition of multiple segments. Here, we performed a chemical genetic screen using zebrafish and discovered that prostaglandins, lipid mediators involved in many physiological functions, influenced pronephros segmentation. Modulating levels of prostaglandin E2 (PGE2) or PGB2restricted distal segment formation and expanded a proximal segment lineage. Perturbation of prostaglandin synthesis by manipulating Cox1 or Cox2 activity altered distal segment formation and was rescued by exogenous PGE2. Disruption of the PGE2receptors Ptger2a and Ptger4a similarly affected the distal segments. Further, changes in Cox activity or PGE2levels affected expression of the transcription factorsirx3bandsim1athat mitigate pronephros segment patterning. These findings show for the first time that PGE2is a regulator of nephron formation in the zebrafish embryonic kidney, thus revealing that prostaglandin signaling may have implications for renal birth defects and other diseases.
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, United States.|Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, United States.
authors.forename: Shahram Jevin
authors.initials: SJ
authors.lastname: Poureetezadi
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, United States.|Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, United States.
authors.forename: Christina N
authors.initials: CN
authors.lastname: Cheng
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, United States.|Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Chambers
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, United States.|Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, United States.
authors.forename: Bridgette E
authors.initials: BE
authors.lastname: Drummond
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, United States.|Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, United States.
authors.forename: Rebecca A
authors.identifier: 0000-0003-3133-7549
authors.initials: RA
authors.lastname: Wingert
mesh_terms: D000818:Animals; D007668:Kidney / Q000196:embryology*; D009399:Nephrons / Q000196:embryology*; D011453:Prostaglandins / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D011453:Prostaglandins
keywords: chemical genetics; developmental biology; kidney; nephrogenesis; nephron; prostaglandins; stem cells; zebrafish