β1 Integrins Control the Formation of Cell Chains in the Adult Rostral Migratory Stream

Belvindrah, Richard; Hankel, Sabine; Walker, John R.; Patton, Bruce L.; Müller, Ulrich

doi:10.1523/jneurosci.2991-06.2007

Cited by 155 publications

(135 citation statements)

References 62 publications

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“…Therefore, the differential migratory response of neuroblasts to HGF stimulation in the SVZ and RMS could result from the activation of different signaling pathways or from the activation of different molecular mediators. Interestingly, ␤1 integrin subunit, which regulates HGF cell invasiveness through cell-matrix interactions (Trusolino et al, 2000;Zhang et al, 2003;Hebrok and Reichardt, 2004), is unevenly distributed along the system (being more expressed in the RMS than in the SVZ) (Belvindrah et al, 2007), suggesting that molecules differentially expressed along the migratory pathway might act synergically with HGF influencing its activity.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte Growth Factor Regulates Migration of Olfactory Interneuron Precursors in the Rostral Migratory Stream through Met-Grb2 Coupling

Garzotto¹,

Giacobini²,

Crepaldi³

et al. 2008

Journal of Neuroscience

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The olfactory bulb is one of the few structures in the mammalian forebrain in which continuous neurogenesis takes place throughout life. Neuronal precursors originate from progenitors located in the subventricular zone (SVZ) of the lateral ventricles, move tangentially in chains through the rostral migratory stream (RMS), and reach the olfactory bulb (OB), where they finally differentiate into granule and glomerular interneurons. Multiple molecular factors are involved in controlling the various steps of this neurogenic process. Here, we show that hepatocyte growth factor (HGF) and its receptor Met protein are expressed in vivo in the OB and throughout the migratory pathway, implying that HGF might mediate migratory signals in this system. By using primary in vitro cultures, we demonstrate that HGF promotes migration of RMS neuroblasts, acting both as an inducer and attractant. HGF stimulation on RMS tissue explants selectively induces MAP kinase pathway activation. Furthermore, in vitro analysis of mice with a point mutation in the Met receptor that impairs signal transduction through the Ras/MAP kinase pathway (Met Grb2/Grb2 ) shows that without Met-Grb2 binding, neuroblast migration is reduced. Overall, these findings indicate that HGF signaling via Met-Grb2 coupling influences olfactory interneuron precursor migration along the RMS.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte Growth Factor Regulates Migration of Olfactory Interneuron Precursors in the Rostral Migratory Stream through Met-Grb2 Coupling

Garzotto¹,

Giacobini²,

Crepaldi³

et al. 2008

Journal of Neuroscience

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“…npg adhesion molecules are involved in initial neuritogenesis [20], neurite outgrowth and regeneration [21], axon path finding [22], neuronal positioning [23][24][25], as well as synaptic development and plasticity [26]. However, whether and how integrin-mediated cell adhesion is involved in neuronal polarization is unknown.…”

Section: Wen-liang Lei Et Al 955mentioning

confidence: 99%

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

et al. 2012

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Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both in vitro and in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.

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“…Close association among NPCs or between NPCs and glial cells within the RMS is believed to be important to maintain chain migration, as disruption to the cell-cell interactions disrupts NPC chain migration. Several classes of adhesion and guidance molecules, such as integrins and laminin, have been identified, which are important for NPC chain migration [3,54,55]. Furthermore, these molecules signal through downstream Rho/ROCK effectors [56][57][58][59].…”

Section: Regulation Of Npc Morphology and Migration By Rho Gtpase Sigmentioning

confidence: 99%

“…For NPCs, molecules such as integrins [3,4] and cell adhesion molecules, such as the NPC marker, polysialated neural cell adhesion molecule (PSA-NCAM) [5][6][7][8][9][10][11], are involved in providing the framework for migration, whereas a number of growth factors, such as epidermal growth factor (EGF) confer the capacity for migration [12,13]. These factors make the cells competent to migrate and may be permissive factors allowing NPCs to respond to directional cues.…”

Section: Introductionmentioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

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Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration.

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β1 Integrins Control the Formation of Cell Chains in the Adult Rostral Migratory Stream

Cited by 155 publications

References 62 publications

Hepatocyte Growth Factor Regulates Migration of Olfactory Interneuron Precursors in the Rostral Migratory Stream through Met-Grb2 Coupling

Hepatocyte Growth Factor Regulates Migration of Olfactory Interneuron Precursors in the Rostral Migratory Stream through Met-Grb2 Coupling

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

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