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 PGB₂ restricted 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 PGE₂ receptors Ptger2a and Ptger4a similarly affected the distal segments. Further, changes in Cox activity or PGE₂ levels affected expression of the transcription factors irx3b and sim1a that mitigate pronephros segment patterning. These findings show for the first time that PGE₂ is 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.

SUBMITTER: Poureetezadi SJ 

PROVIDER: S-EPMC5173325 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature