title: EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDia1 and mDia3 in combination.
abstract: mDia is an actin nucleator and polymerization factor regulated by the small GTPase Rho and consists of three isoforms. Here, we found that mice lacking mDia1 and mDia3, two isoforms expressed in the brain, in combination (mDia-DKO mice) show impaired left-right limb coordination during locomotion and aberrant midline crossing of axons of corticospinal neurons and spinal cord interneurons. Given that mice lacking Ephrin-B3-EphA4 signaling show a similar impairment in locomotion, we examined whether mDia is involved in Ephrin-B3-EphA4 signaling for axon repulsion. In primary cultured neurons, mDia deficiency impairs growth cone collapse and axon retraction induced by chemo-repellants including EphA ligands. In mDia-DKO mice, the Ephrin-B3-expressing midline structure in the spinal cord is disrupted, and axons aberrantly cross the spinal cord midline preferentially through the region devoid of Ephrin-B3. Therefore, mDia plays multiple roles in the proper formation of the neural network in vivo.
authors.affiliation: Department of Pharmacology, Kyoto University Graduate School of Medicine, Yoshida-konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Ryota
authors.initials: R
authors.lastname: Shinohara
authors.forename: Dean
authors.initials: D
authors.lastname: Thumkeo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamijo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimaru
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hioki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D036389:Ephrin-B3 / Q000378:metabolism*; D005552:Forelimb / Q000502:physiology; D000080865:Formins; D005684:Gait / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D036122:Receptor, EphA4 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C491464:Diap1 protein, mouse; C491463:Diap2 protein, mouse; D036389:Ephrin-B3; D000080865:Formins; D036122:Receptor, EphA4