title: Identity of neocortical layer 4 neurons is specified through correct positioning into the cortex.
abstract: Many cell-intrinsic mechanisms have been shown to regulate neuronal subtype specification in the mammalian neocortex. However, how much cell environment is crucial for subtype determination still remained unclear. Here, we show that knockdown of Protocadherin20 (Pcdh20), which is expressed in post-migratory neurons of layer 4 (L4) lineage, caused the cells to localize in L2/3. The ectopically positioned "future L4 neurons" lost their L4 characteristics but acquired L2/3 characteristics. Knockdown of a cytoskeletal protein in the future L4 neurons, which caused random disruption of positioning, also showed that those accidentally located in L4 acquired the L4 characteristics. Moreover, restoration of positioning of the Pcdh20-knockdown neurons into L4 rescued the specification failure. We further suggest that the thalamocortical axons provide a positional cue to specify L4 identity. These results suggest that the L4 identity is not completely determined at the time of birth but ensured by the surrounding environment after appropriate positioning.
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Division of Visual Information Processing, National Institute for Physiological Sciences, National Institutes for Natural Sciences, Okazaki, Japan.|Department of Physiological Sciences, Graduate University for Advanced Studies, Okazaki, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nakagawa
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kashiko
authors.initials: K
authors.lastname: Tachikawa
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Aramaki
authors.affiliation: Department of Cell Biology, Kansai Medical University, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirano
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Division of Visual Information Processing, National Institute for Physiological Sciences, National Institutes for Natural Sciences, Okazaki, Japan.|Department of Physiological Sciences, Graduate University for Advanced Studies, Okazaki, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshimura
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazunori
authors.identifier: http://orcid.org/0000-0003-1864-9425
authors.initials: K
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D008813:Mice, Inbred ICR; D019579:Neocortex / Q000033:anatomy & histology* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification* / Q000502:physiology*; D000091363:Protocadherins
chemical_list: D015820:Cadherins; D009419:Nerve Tissue Proteins; C527873:PCDH20 protein, mouse; D000091363:Protocadherins
keywords: cell fate; cerebral cortex; cortical layer; developmental biology; mouse; neuroscience; protocadherin; stem cells