title: Rac1-mediated indentation of resting neurons promotes the chain migration of new neurons in the rostral migratory stream of post-natal mouse brain.
abstract: New neurons generated in the ventricular-subventricular zone in the post-natal brain travel toward the olfactory bulb by using a collective cell migration process called 'chain migration.' These new neurons show a saltatory movement of their soma, suggesting that each neuron cycles through periods of 'rest' during migration. Here, we investigated the role of the resting neurons in chain migration using post-natal mouse brain, and found that they undergo a dynamic morphological change, in which a deep indentation forms in the cell body. Inhibition of Rac1 activity resulted in less indentation of the new neurons in vivo. Live cell imaging using a Förster resonance energy transfer biosensor revealed that Rac1 was activated at the sites of contact between actively migrating and resting new neurons. On the cell surface of resting neurons, Rac1 activation coincided with the formation of the indentation. Furthermore, Rac1 knockdown prevented the indentation from forming and impaired migration along the resting neurons. These results suggest that Rac1 regulates a morphological change in the resting neurons, which allows them to serve as a migratory scaffold, and thereby non-cell-autonomously promotes chain migration.
authors.affiliation: Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hikita
authors.forename: Akihisa
authors.initials: A
authors.lastname: Ohno
authors.forename: Masato
authors.initials: M
authors.lastname: Sawada
authors.forename: Haruko
authors.initials: H
authors.lastname: Ota
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Sawamoto
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology* / Q000254:growth & development; D009924:Organ Culture Techniques; D059008:Time-Lapse Imaging; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: Rho family small GTPase; adult neurogenesis; collective cell migration