title: TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
abstract: Retinal axon specification and growth are critically sensitive to the dosage of numerous signaling molecules and transcription factors. Subtle variations in the expression levels of key molecules may result in a variety of axonal growth anomalies. miR-181a and miR-181b are two eye-enriched microRNAs whose inactivation in medaka fish leads to alterations of the proper establishment of connectivity and function in the visual system. miR-181a/b are fundamental regulators of MAPK signaling and their role in retinal axon growth and specification is just beginning to be elucidated. Here we demonstrate that miR-181a/b are key nodes in the interplay between TGF-β and MAPK/ERK within the functional pathways that control retinal axon specification and growth. Using a variety of in vivo and in vitro approaches in medaka fish, we demonstrate that TGF-β signaling controls the miR-181/ERK regulatory network, which in turn strengthens the TGF-β-mediated regulation of RhoA degradation. Significantly, these data uncover the role of TGF-β signaling in vivo, for the first time, in defining the correct wiring and assembly of functional retina neural circuits and further highlight miR-181a/b as key factors in axon specification and growth.
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Carrella
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Barbato
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
authors.forename: Ylenia
authors.initials: Y
authors.lastname: D'Agostino
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Salierno
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Manfredi
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.|Medical Genetics, Dipartimento di Biochimica, Biofisica e Patologia Generale, Second University of Naples, via Luigi De Crecchio 7, 80138, Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.affiliation: Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Conte
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D029941:Fish Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D009990:Oryzias / Q000196:embryology*; D012160:Retina / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D020742:rhoA GTP-Binding Protein