TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.

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...

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Main Authors: Sabrina Carrella, Sara Barbato, Ylenia D'Agostino, Francesco Giuseppe Salierno, Anna Manfredi, Sandro Banfi, Ivan Conte
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0144129
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author Sabrina Carrella
Sara Barbato
Ylenia D'Agostino
Francesco Giuseppe Salierno
Anna Manfredi
Sandro Banfi
Ivan Conte
author_facet Sabrina Carrella
Sara Barbato
Ylenia D'Agostino
Francesco Giuseppe Salierno
Anna Manfredi
Sandro Banfi
Ivan Conte
author_sort Sabrina Carrella
collection DOAJ
description 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.
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spelling doaj-art-6da45016465e45529806b14cb858df072025-08-20T02:34:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014412910.1371/journal.pone.0144129TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.Sabrina CarrellaSara BarbatoYlenia D'AgostinoFrancesco Giuseppe SaliernoAnna ManfrediSandro BanfiIvan ConteRetinal 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.https://doi.org/10.1371/journal.pone.0144129
spellingShingle Sabrina Carrella
Sara Barbato
Ylenia D'Agostino
Francesco Giuseppe Salierno
Anna Manfredi
Sandro Banfi
Ivan Conte
TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
PLoS ONE
title TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
title_full TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
title_fullStr TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
title_full_unstemmed TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
title_short TGF-β Controls miR-181/ERK Regulatory Network during Retinal Axon Specification and Growth.
title_sort tgf β controls mir 181 erk regulatory network during retinal axon specification and growth
url https://doi.org/10.1371/journal.pone.0144129
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