miR-181a/b control the assembly of visual circuitry by regulating retinal axon specification and growth.
Connectivity and function of neuronal circuitry require the correct specification and growth of axons and dendrites. Here, we identify the microRNAs miR-181a and miR-181b as key regulators of retinal axon specification and growth. Loss of miR-181a/b in medaka fish (Oryzias latipes) failed to consolidate amacrine cell processes into axons and delayed the growth of retinal ganglion cell (RGC) axons. These alterations were accompanied by defects in visual connectivity and function. We demonstrated that miR-181a/b exert these actions through negative modulation of MAPK/ERK signaling that in turn leads to RhoA reduction and proper neuritogenesis in both amacrine cells and RGCs via local cytoskeletal rearrangement. Our results identify a new pathway for axon specification and growth unraveling a crucial role of miR-181a/b in the proper establishment of visual system connectivity and function.
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
Sabrina
S
Carrella
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
Ylenia
Y
D'Agostino
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
Sara
S
Barbato
Institute of Molecular Life Sciences, Division of Neurobiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Sabina P
SP
Huber-Reggi
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
Francesco G
FG
Salierno
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
Anna
A
Manfredi
Institute of Molecular Life Sciences, Division of Neurobiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Stephan C F
SC
Neuhauss
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.|Medical Genetics, Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via Luigi De Crecchio 7, 80138, Naples, Italy.
Sandro
S
Banfi
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli (Naples), 80078, Italy.
Ivan
I
Conte
D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D049108:Cell Enlargement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D029941:Fish Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009990:Oryzias; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development* / Q000503:physiopathology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D029941:Fish Proteins; D035683:MicroRNAs; D020742:rhoA GTP-Binding Protein
MAPK signaling; axon specification; miR-181a; miR-181b; retina