The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos

• Published in: Communications biology 2021-10, Vol.4 (1), p.1158-1158, Article 1158
• Main Authors: Massé, Karine, Bhamra, Surinder, Paroissin, Christian, Maneta-Peyret, Lilly, Boué-Grabot, Eric, Jones, Elizabeth A.
• Format: Article
• Language: English
• Subjects: 13; 13/51; 38/32; 38/70; 631/136; 631/136/1455; 631/136/2060; 64/114; 82; Animals; Biology; Biomedical and Life Sciences; Body Patterning - genetics; Ectonucleotidase; Embryo, Nonmammalian - embryology; Embryonic Development; Embryos; Gene Regulatory Networks; Hybridization; Kidney - embryology; Kidney - physiology; Kidneys; Life Sciences; Lipids; Membrane proteins; Neurobiology; Neurons and Cognition; Overexpression; Phosphatidylserine; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - physiology; Physiology; Proteins; Purines; Roles; Signal Transduction; Wnt protein; Xenopus; Xenopus laevis - genetics; Xenopus laevis - growth & development; Xenopus laevis - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - physiology
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02688-9

The enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation in Xenopus . Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for pronephric markers expression and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and non-catalytic mechanism by which lipidic signalling regulates nephrogenesis. Massé and colleagues identify enpp4 as a key regulator in the development of the kidney in Xenopus . The gene signalling pathways regulated by this ectonucleotidase are described and lipidic signalling regulatory mechanisms are explored.