Neuroblast Division during Migration toward the Ischemic Striatum: A Study of Dynamic Migratory and Proliferative Characteristics of Neuroblasts from the Subventricular Zone

Zhang, Rui Lan; LeTourneau, Yvonne; Gregg, Sara R; Wang, Ying; Toh, Yier; Robin, Adam; Zhang, Zheng Gang; Chopp, Michael

doi:10.1523/jneurosci.4969-06.2007

Cited by 116 publications

(106 citation statements)

References 29 publications

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“…We also counted the number of DCX-, CldU-, and IdU-positive cells and found that 13.89% (n = 3), 12.5% (n = 4), 13.6% (n = 4), and 18.3% (n = 4) of double labeled with CldU and IdU cells were DCX + at 2, 4, 7, and 14 days after stroke, respectively. These data suggest that a sub-population of migrating neuroblasts is within the cell cycle, which is consistent with previous findings that migrating neuroblasts proliferate (Menezes et al, 1995;Luskin et al, 1997;Wichterle et al, 1997;Zhang et al, 2007a).…”

Section: Stroke Alters P and Q Fractions Of Neural Progenitor Cellssupporting

confidence: 93%

Lengthening the G₁ Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Zhang

Roberts

et al. 2007

J Cereb Blood Flow Metab

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The proportion of neural progenitors that remain in (P fraction) and exit from (Q fraction) the cell cycle determines the degree of neurogenesis. Using S-phase labeling with 5-bromo-2 0 -deoxyuridine and a double nucleoside analog-labeling scheme, we measured the cell-cycle kinetics of neural progenitors and estimated the proportion of P and Q fractions in the subventricular zone (SVZ) of adult rats subjected to stroke. Stroke increased SVZ cell proliferation, starting 2 days, reaching a maximum 4 and 7 days after stroke. The cell-cycle length (T C ) of SVZ cells changed dynamically over a period of 2 to 14 days after stroke, with the shortest length of 11 h at 2 days after stroke. The reduction of the T C resulted from a decrease of the G 1 phase because the G 2 , M, and S phases were unchanged. In addition, during this period, reduction of the G 1 phase was concomitant with an increase in the P fraction, whereas an augmentation of the Q fraction was associated with lengthening of the G 1 phase. Furthermore, approximately 90% of cells that exited the cell cycle were neurons and the population of a pair of dividing daughter cells with a neuronal marker increased from 9% at 2 days to 26% at 14 days after stroke. These data suggest that stroke triggers early expansion of the progenitor pool via shortening the cell-cycle length and retaining daughter cells within the cell cycle, and the lengthening of G 1 leads to daughter cells exiting the cell cycle and differentiating into neurons.

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Section: Stroke Alters P and Q Fractions Of Neural Progenitor Cellssupporting

confidence: 93%

Lengthening the G₁ Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Zhang

Roberts

et al. 2007

J Cereb Blood Flow Metab

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“…The antigenic properties of neuroblasts in rat SVZ were partly different from those in mice (Doetsch et al, 1997). EGFR and PDGFRa were localized on the centriole and primary cilium of neuroblasts, possibly mediating their retained proliferative capacity (Zhang et al, 2007). In accordance, neuroblasts incorporated BrdU after both short-and long-term administration.…”

Section: Discussionmentioning

confidence: 90%

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

Danilov

Gomes-Leal

Ahlenius

et al. 2008

Glia

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Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate olfactory bulb interneurons in the adult rodent brain. Based on their ultrastructural and antigenic properties, NSCs, transient amplifying precursor cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ ultrastructurally and at the light microscopy level, and to determine the antigenic properties of each cell type using gold and fluorescence immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal cells, displaced ependymal cells, and mature astrocytes. In contrast, transient amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts had epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFRa) expressed on the ciliary apparatus and were the only cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR and PDGFRa were associated with the microtubule of the mitotic spindle. Ependymal and displaced ependymal cells also expressed EGFR and PDGFRa on their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs disassemble the primary cilium and symmetrically distribute EGFR and PDGFRa among their progeny. V

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“…Ischemic stroke induced neurogenesis in the rodent SVZ [1,72,73] and stimulated newborn precursor migration to the peri-infarct regions [74,75]. This migration may be induced by SDF-1/CXCL4, which plays a role in directing newborn neurons toward an ischemic lesion [76] and may be enhanced by release of mitogenic factors, such as EGF [77,78].…”

Section: Regulation Of Npc Migration To Sites Of Neural Damagementioning

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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Neuroblast Division during Migration toward the Ischemic Striatum: A Study of Dynamic Migratory and Proliferative Characteristics of Neuroblasts from the Subventricular Zone

Abstract: Collectively, the present study suggests that stroke promotes cytokinesis of migrating neuroblasts, and these cells migrate toward the ischemic striatum with distinct migratory behaviors and retain the capacity for cell division during migration.

Cited by 116 publications

References 29 publications

Lengthening the G₁ Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Lengthening the G₁ Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

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Neuroblast Division during Migration toward the Ischemic Striatum: A Study of Dynamic Migratory and Proliferative Characteristics of Neuroblasts from the Subventricular Zone

Abstract: Collectively, the present study suggests that stroke promotes cytokinesis of migrating neuroblasts, and these cells migrate toward the ischemic striatum with distinct migratory behaviors and retain the capacity for cell division during migration.

Cited by 116 publications

References 29 publications

Lengthening the G1 Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Lengthening the G1 Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

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Product

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Lengthening the G₁ Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

Lengthening the G₁ Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke