title: Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells.
abstract: The retinoblastoma protein (RB) is essential for normal cell cycle control. RB function depends, at least in part, on interactions with the E2F family of DNA-binding transcription factors (E2Fs). To study the role of RB in the adult testis, a Sertoli cell (SC)-specific Rb knockout mouse line (SC-RbKO) was generated using the Cre/loxP recombination system. SC-RbKO mice exhibited an age-dependent testicular atrophy, impaired fertility, severe SC dysfunction, and spermatogenic defects. Removal of Rb in SC induced aberrant SC cycling, dedifferentiation, and apoptosis. Here we show that E2F3 is the only E2F expressed in mouse SCs and that RB interacts with E2F3 during mouse testicular development. In the absence of RB, the other retinoblastoma family members p107 and p130 began interacting with E2F3 in the adult testes. In vivo silencing of E2F3 partially restored the SC maturation and survival as well as spermatogenesis in the SC-RbKO mice. These results point to RB as a key regulator of SC function in adult mice and that the RB/E2F3 pathway directs SC maturation, cell cycle quiescence, and RB protects SC from apoptosis.
authors.affiliation: 1] Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland [2] Department of Pediatrics, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Rotgers
authors.affiliation: Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Rivero-Müller
authors.affiliation: 1] Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland [2] Department of Pediatrics, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Nurmio
authors.affiliation: Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Parvinen
authors.affiliation: INRA-CNRS-Haras Nationaux-Université de Tours Joint Research Unit for Reproductive and Behavioural Physiology, Tours Research Centre, Nouzilly 3780, France.
authors.forename: F
authors.initials: F
authors.lastname: Guillou
authors.affiliation: 1] Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland [2] Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
authors.forename: I
authors.initials: I
authors.lastname: Huhtaniemi
authors.affiliation: Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Kotaja
authors.affiliation: 1] Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland [2] Biotechnology Department, College of Graduate Studies, Arabian Gulf University, PO BOX 26670 Manama, Bahrain.
authors.forename: S
authors.initials: S
authors.lastname: Bourguiba-Hachemi
authors.affiliation: 1] Department of Physiology, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland [2] Department of Pediatrics, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Toppari
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D050699:E2F3 Transcription Factor; C490840:E2f3 protein, mouse; D016160:Retinoblastoma Protein