title: Ectopic Reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex.
abstract: Neurons in the developing mammalian neocortex form the cortical plate (CP) in an "inside-out" manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal-Retzius neurons in the marginal zone (MZ), is crucial for this "inside-out" layering, because the layers are inverted in the Reelin-deficient mouse, reeler (Reln(rl)). Even though more than a decade has passed since the discovery of reelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in the reeler cortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent "inside-out" alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent "inside-out" alignment of neurons independently of other factors/structures near the MZ.
authors: Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Ken-ichiro
authors: K
authors: Kubo
authors: Takao
authors: T
authors: Honda
authors: Kenji
authors: K
authors: Tomita
authors: Katsutoshi
authors: K
authors: Sekine
authors: Kazuhiro
authors: K
authors: Ishii
authors: Asuka
authors: A
authors: Uto
authors: Kazuma
authors: K
authors: Kobayashi
authors: Hidenori
authors: H
authors: Tabata
authors: Kazunori
authors: K
authors: Nakajima
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002449:Cell Aggregation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D019579:Neocortex / Q000196:embryology* / Q000502:physiology* / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases