title: Cadherin-7 regulates mossy fiber connectivity in the cerebellum.
abstract: To establish highly precise patterns of neural connectivity, developing axons must stop growing at their appropriate destinations and specifically synapse with target cells. However, the molecular mechanisms governing these sequential steps remain poorly understood. Here, we demonstrate that cadherin-7 (Cdh7) plays a dual role in axonal growth termination and specific synapse formation during the development of the cerebellar mossy fiber circuit. Cdh7 is expressed in mossy fiber pontine nucleus (PN) neurons and their target cerebellar granule neurons during synaptogenesis and selectively mediates synapse formation between those neurons. Additionally, Cdh7 presented by mature granule neurons diminishes the growth potential of PN axons. Furthermore, knockdown of Cdh7 in PN neurons in vivo severely impairs the connectivity of PN axons in the developing cerebellum. These findings reveal a mechanism by which a single bifunctional cell-surface receptor orchestrates precise wiring by regulating axonal growth potential and synaptic specificity.
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: kuwako@z2.keio.jp.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Kuwako
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishimoto
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawase
authors.affiliation: Division of Regenerative Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Hirotaka James
authors.initials: HJ
authors.lastname: Okano
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: hidokano@a2.keio.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009412:Nerve Fibers / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D015820:Cadherins; C501012:Cdh7 protein, mouse