title: Type II cadherins guide assembly of a direction-selective retinal circuit.
abstract: Complex retinal circuits process visual information and deliver it to the brain. Few molecular determinants of synaptic specificity in this system are known. Using genetic and optogenetic methods, we identified two types of bipolar interneurons that convey visual input from photoreceptors to a circuit that computes the direction in which objects are moving. We then sought recognition molecules that promote selective connections of these cells with previously characterized components of the circuit. We found that the type II cadherins, cdh8 and cdh9, are each expressed selectively by one of the two bipolar cell types. Using loss- and gain-of-function methods, we showed that they are critical determinants of connectivity in this circuit and that perturbation of their expression leads to distinct defects in visually evoked responses. Our results reveal cellular components of a retinal circuit and demonstrate roles of type II cadherins in synaptic choice and circuit function.
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Krishnaswamy
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: De la Huerta
authors.affiliation: Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: sanesj@mcb.harvard.edu.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D051379:Mice; D012160:Retina / Q000166:cytology / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000378:metabolism*; D013569:Synapses; D014795:Visual Pathways
chemical_list: D015820:Cadherins; C504541:Cdh8 protein, mouse; C561947:cadherin-9, mouse