title: Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders.
abstract: Using comparative genomic hybridization analysis for an autism spectrum disorder (ASD) patient, a 73-Kb duplication at 19q13.33 (nt. 49 562 755-49 635 956) including LIN7B and 5 other genes was detected. We then identified a novel frameshift mutation in LIN7B in another ASD patient. Since LIN7B encodes a scaffold protein essential for neuronal function, we analyzed the role of Lin-7B in the development of cerebral cortex. Acute knockdown of Lin-7B with in utero electroporation caused a delay in neuronal migration during corticogenesis. When Lin-7B was knocked down in cortical neurons in one hemisphere, their axons failed to extend efficiently into the contralateral hemisphere after leaving the corpus callosum. Meanwhile, enhanced expression of Lin-7B had no effects on both cortical neuron migration and axon growth. Notably, silencing of Lin-7B did not affect the proliferation of neuronal progenitors and stem cells. Taken together, Lin-7B was found to play a pivotal role in corticogenesis through the regulation of excitatory neuron migration and interhemispheric axon growth, while further analyses are required to directly link functional defects of Lin-7B to ASD pathophysiology. Lin-7 plays a pivotal role as a scaffold protein in synaptic development and plasticity. Based on genetic analyses we identified mutations in LIN-7B gene in some ASD (autism-spectrum disorder) patients. Functional defects in Lin-7B caused abnormal neuronal migration and interhemispheric axon growth during mouse brain development. Thus, functional deficiency in Lin-7B could be implicated in clinical phenotypes in some ASD patients through bringing about abnormal cortical architecture.
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizuno
authors.forename: Ayumi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Nanako
authors.initials: N
authors.lastname: Hamada
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Eriko F
authors.initials: EF
authors.lastname: Jimbo
authors.forename: Mariko Y
authors.initials: MY
authors.lastname: Momoi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tabata
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D001921:Brain / Q000254:growth & development*; D019556:COS Cells; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002522:Chlorocebus aethiops; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D011247:Pregnancy; D034622:RNA Interference
chemical_list: C114671:LIN7B protein, human; D008565:Membrane Proteins; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Lin-7B; autism; cerebral cortex; development; neuronal migration