title: Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity.
abstract: Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yonehara
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering of ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: Fiscella
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Antonia
authors.initials: A
authors.lastname: Drinnenberg
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Esposti
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Stuart
authors.initials: S
authors.lastname: Trenholm
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Krol
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering of ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Franke
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Brigitte Gross
authors.initials: BG
authors.lastname: Scherf
authors.affiliation: Department of Ophthalmology, Semmelweis University, Mária u. 39, 1085 Budapest, Hungary.
authors.forename: Akos
authors.initials: A
authors.lastname: Kusnyerik
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering of ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Müller
authors.affiliation: Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Tűzoltó u. 58, 1094 Budapest, Hungary.
authors.forename: Arnold
authors.initials: A
authors.lastname: Szabo
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Josephine
authors.initials: J
authors.lastname: Jüttner
authors.affiliation: Laboratory and Animal Services, Novartis Institute for Biomedical Research, Fabrikstrasse 28, 4056 Basel, Switzerland.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cordoba
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Ashrithpal Police
authors.initials: AP
authors.lastname: Reddy
authors.affiliation: Department of Ophthalmology, Semmelweis University, Mária u. 39, 1085 Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Németh
authors.affiliation: Department of Ophthalmology, Semmelweis University, Mária u. 39, 1085 Budapest, Hungary.
authors.forename: Zoltán Zsolt
authors.initials: ZZ
authors.lastname: Nagy
authors.affiliation: Jules-Gonin Eye Hospital, Avenue de France 15, 1000 Lausanne, Switzerland.
authors.forename: Francis
authors.initials: F
authors.lastname: Munier
authors.affiliation: Bio Engineering Laboratory, Department of Biosystems Science and Engineering of ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Department of Ophthalmology, University of Basel, Mittlere Strasse 91, 4031 Basel, Switzerland. Electronic address: botond.roska@fmi.ch.
authors.forename: Botond
authors.initials: B
authors.lastname: Roska
mesh_terms: D000200:Action Potentials / Q000502:physiology; D025042:Amacrine Cells / Q000166:cytology*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008822:Mice, Transgenic; D009039:Motion Perception / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D020417:Nystagmus, Congenital / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D012160:Retina / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology; D013569:Synapses / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; C547741:FRMD7 protein, mouse