Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells
2014
Rotgers, E. | Rivero-Müller, A. | Nurmio, M. | Parvinen, M. | Guillou, Florian Jean Louis | Huhtaniemi, I. | Kotaja, N. | Bourguiba-Hachemi, S. | Toppari, J. | Department of Physiology ; University of Turku | Department of Physiology, Department of Pediatrics ; University of Turku | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) | Department of Surgery and Cancer ; Imperial College London | College of Graduate Studies, Biotechnology Department ; Arabian Gulf University | Academy of Finland, The Sigrid Jusélius Foundation, The Finish Cultural Foundation, Turku Doctoral Programme of Molecular Medicine (TuDMM), and The Turku University Hospital evo-funds
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.
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