title: Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex.
abstract: Neuronal migration is critical for establishing neocortical cell layers and migration defects can cause neurological and psychiatric diseases. Recent studies show that radially migrating neocortical neurons use glia-dependent and glia-independent modes of migration, but the signaling pathways that control different migration modes and the transitions between them are poorly defined. Here, we show that Dab1, an essential component of the reelin pathway, is required in radially migrating neurons for glia-independent somal translocation, but not for glia-guided locomotion. During migration, Dab1 acts in translocating neurons to stabilize their leading processes in a Rap1-dependent manner. Rap1, in turn, controls cadherin function to regulate somal translocation. Furthermore, cell-autonomous neuronal deficits in somal translocation are sufficient to cause severe neocortical lamination defects. Thus, we define the cellular mechanism of reelin function during radial migration, elucidate the molecular pathway downstream of Dab1 during somal translocation, and establish the importance of glia-independent motility in neocortical development.
authors.affiliation: Dorris Neuroscience Center and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Santos J
authors.initials: SJ
authors.lastname: Franco
authors.forename: Isabel
authors.initials: I
authors.lastname: Martinez-Garay
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Sanz
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Harkins-Perry
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D055879:Gene Knock-In Techniques; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D019579:Neocortex / Q000196:embryology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D015820:Cadherins; C489083:Cdh2 protein, mouse; D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D020827:rap1 GTP-Binding Proteins