β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain.
Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan; Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Teppei
T
Fujioka
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Naoko
N
Kaneko
Center for Brain Integration Research, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Itsuki
I
Ajioka
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Kanako
K
Nakaguchi
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Taichi
T
Omata
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Honoka
H
Ohba
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Reinhard
R
Fässler
Laboratory of Comparative Neurobiology, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia 46980, Spain; Multiple Sclerosis and Neural Regeneration Unit, IIS Hospital La Fe, Valencia 46026, Spain.
José Manuel
JM
García-Verdugo
Division of Matrixome Research and Application, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
Kiyotoshi
K
Sekiguchi
Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Noriyuki
N
Matsukawa
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan; Division of Neural Development and Regeneration, National Institute of Physiological Sciences, Okazaki, Aichi 444-8585, Japan. Electronic address: sawamoto@med.nagoya-cu.ac.jp.
Kazunobu
K
Sawamoto
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D020521:Stroke / Q000378:metabolism; D054457:Tissue Scaffolds
D019012:Integrin beta1; D007797:Laminin
Blood vessel; Chain migration; Laminin; Stroke; Vasculature-guided migration; β1 integrin