title: How does Reelin control neuronal migration and layer formation in the developing mammalian neocortex?
abstract: The mammalian neocortex has a laminar structure that develops in a birth-date-dependent "inside-out" pattern. Its layered structure is established by neuronal migration accompanied by sequential changes in migratory mode regulated by several signaling cascades. Although Reelin was discovered about two decades ago and is one of the best known molecules that is indispensable to the establishment of the "inside-out" neuron layers, the cellular and molecular functions of Reelin in layer formation are still largely unknown. In this review article, we summarize our recent understanding of Reelin's functions during neuronal migration. Reelin acts in at least two different steps of neuronal migration: the final step of neuronal migration (somal/terminal translocation) just beneath the marginal zone (MZ) and the regulation of cell polarity step when the neurons change their migratory mode from multipolar migration to locomotion. During the translocation mode, Reelin activates integrin α5β1 through an intracellular pathway that triggers the translocation and activates N-cadherin in concert with the nectin-afadin system. Reelin is also involved in the termination of neuronal migration by degrading Dab1 via the SOCS7-Cullin5-Rbx2 system, and Reelin has been found to induce the birth-date-dependent neuronal aggregation in vivo. Based on these findings, we hypothesize that the molecular function of Reelin during neuronal migration is to control cell-adhesiveness during development by regulating the expression/activation of cell adhesion molecules.
authors: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors: Katsutoshi
authors: K
authors: Sekine
authors: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors: Ken-ichiro
authors: K
authors: Kubo
authors: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: kazunori@z6.keio.jp.
authors: Kazunori
authors: K
authors: Nakajima
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D008322:Mammals / Q000033:anatomy & histology* / Q000254:growth & development; D019579:Neocortex / Q000166:cytology* / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: Cell adhesion molecules; Dab1; Inside-out; Primitive cortical zone; Reelin; Terminal translocation