title: Linx mediates interaxonal interactions and formation of the internal capsule.
abstract: During the development of forebrain connectivity, ascending thalamocortical and descending corticofugal axons first intermingle at the pallial-subpallial boundary to form the internal capsule (IC). However, the identity of molecular cues that guide these axons remains largely unknown. Here, we show that the transmembrane protein Linx is robustly expressed in the prethalamus and lateral ganglionic eminence-derived corridor and on corticofugal axons, but not on thalamocortical axons, and that mice with a null mutation of Linx exhibit a complete absence of the IC. Moreover, regional inactivation of Linx either in the prethalamus and LGE or in the neocortex leads to a failure of IC formation. Furthermore, Linx binds to thalamocortical projections, and it promotes outgrowth of thalamic axons. Thus, Linx guides the extension of thalamocortical axons in the ventral forebrain, and subsequently, it mediates reciprocal interactions between thalamocortical and corticofugal axons to form the IC.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. Electronic address: mandai@med.kobe-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mandai
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Dorothy V
authors.initials: DV
authors.lastname: Reimert
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: david_ginty@hms.harvard.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Ginty
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D020772:Internal Capsule / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009924:Organ Culture Techniques; D016548:Prosencephalon / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D013788:Thalamus / Q000502:physiology*
chemical_list: C544153:Linx protein, mouse; D009419:Nerve Tissue Proteins