Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors

Liu, Xiuxin; Wang, Qin; Haydar, Tarik F.; Bordey, Angélique

doi:10.1038/nn1522

Cited by 399 publications

(479 citation statements)

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“…Previous work demonstrated that GABA is involved in the control of OB neurogenesis by regulating proliferation and migration of neuronal precursors in the rostral migratory stream (Bolteus and Bordey, 2004;Liu et al, 2005). Our findings extend the role of GABA to the control of dendritic initiation.…”

Section: Discussionsupporting

confidence: 82%

GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb

Gascon¹,

Dayer²,

Sauvain³

et al. 2006

J. Neurosci.

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The initial formation and growth of dendrites is a critical step leading to the integration of newly generated neurons into postnatal functional networks. However, the cellular mechanisms and extracellular signals regulating this process remain mostly unknown. By directly observing newborn neurons derived from the subventricular zone in culture as well as in olfactory bulb slices, we show that ambient GABA acting through GABA A receptors is essential for the temporal stability of lamellipodial protrusions in dendritic growth cones but did not interfere with filopodia dynamics. Furthermore, we provide direct evidence that ambient GABA is required for the proper initiation and elongation of dendrites by promoting the rapid stabilization of new dendritic segments after their extension. The effects of GABA on the initial formation of dendrites depend on depolarization and Ca 2ϩ influx and are associated with a higher stability of microtubules. Together, our results indicate that ambient GABA is a key regulator of dendritic initiation in postnatally generated olfactory interneurons and offer a mechanism by which this neurotransmitter drives early dendritic growth.

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Section: Discussionsupporting

confidence: 82%

GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb

Gascon¹,

Dayer²,

Sauvain³

et al. 2006

J. Neurosci.

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“…This suggests that distinct precursor cell populations respond to glutamate/GABA in different ways. In adult SVZa, glutamate and GABA have been reported to exert opposing effects on progenitor cells: glutamate activates (Brazel et al, 2005) while GABA inhibits (Liu et al, 2005) their proliferation. There- fore, it is possible to speculate that these two endogenous amino acids may differentially affect neural or neuronal progenitors in monkey SVZa to achieve precursor cell proliferation/differentiation with either retention in SVZa or migration toward the olfactory bulb.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Tonchev¹,

Yamashima²,

Sawamoto³

2006

Neuroscience

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Abstract-The anterior subventricular zone of the adult mammalian brain contains progenitor cells which are upregulated after cerebral ischemia. We have previously reported that while a part of the progenitors residing in adult monkey anterior subventricular zone travels to the olfactory bulb, many of these cells sustain location in the anterior subventricular zone for months after injury, exhibiting a phenotype of either neural or neuronal precursors. Here we show that ischemia increased the numbers of anterior subventricular zone progenitor cells expressing developmentally regulated transcription factors including Pax6 (paired-box 6), Emx2 (empty spiracles-homeobox 2), Sox 1-3 (sex determining region Y-box 1-3), Ngn1 (neurogenin 1), Dlx1,5 (distalless-homeobox 1,5), Olig1,3 (oligodendrocyte lineage gene 1,3) and Nkx2.2 (Nk-box 2.2), as compared with control brains. Analysis of transcription factor protein expression by sustained neural or neuronal precursors in anterior subventricular zone revealed that these two cell types were positive for characteristic sets of transcription factors. The proteins Pax6, Emx2, Sox2,3 and Olig1 were predominantly localized to dividing neural precursors while the factors Sox1, Ngn1, Dlx1,5, Olig2 and Nkx2.2 were mainly expressed by neuronal precursors. Further, differences between monkeys and non-primate mammals emerged, related to expression patterns of Pax6, Olig2 and Dlx2. Our results suggest that a complex network of developmental signals might be involved in the specification of primate progenitor cells.

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“…However, the opposite effect has been reported for secondary progenitors located in the embryonic subventricular zone [3], where GABA A R activation reduces DNA synthesis/mitosis possibly via depolarization-mediated Ca 2þ entry [4]. GABA signaling exerts a complex regulation also in the adult subependymal zone (SEZ) where neuroblasts and glial fibrillary acidic protein (GFAP)-expressing cells, which include stem cells as well as astrocytes, regulate ambient GABA levels, by mediating its nonsynaptic release and uptake, respectively [5]. In turn, GABA A R activation downregulates neuroblast proliferation and migration [6][7][8].…”

Section: Introductionmentioning

confidence: 98%

“…In turn, GABA A R activation downregulates neuroblast proliferation and migration [6][7][8]. Activation of GABA A R also inhibits the proliferation of GFAP-expressing cells in the adult niche [5]. However, the cellular mechanisms underlying these effects are still unclear.…”

Section: Introductionmentioning

confidence: 99%

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

et al. 2011

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Signal-regulated changes in cell size affect cell division and survival and therefore are central to tissue morphogenesis and homeostasis. In this respect, GABA receptors (GABA A Rs) are of particular interest because allowing anions flow across the cell membrane modulates the osmolyte flux and the cell volume. Therefore, we have here investigated the hypothesis that GABA may regulate neural stem cell proliferation by inducing cell size changes. We found that, besides neuroblasts, also neural precursors in the neonatal murine subependymal zone sense GABA via GABA A Rs. However, unlike in neuroblasts, where it induced depolarization-mediated [Ca 21 ] i increase, GABA A Rs activation in precursors caused hyperpolarization. This resulted in osmotic swelling and increased surface expression of epidermal growth factor receptors (EGFRs). Furthermore, activation of GABA A Rs signaling in vitro in the presence of EGF modified the expression of the cell cycle regulators, phosphatase and tensin homolog and cyclin D1, increasing the pool of cycling precursors without modifying cell cycle length. A similar effect was observed on treatment with diazepam. We also demonstrate that GABA and diazepam responsive precursors represent prominin 1 stem cells. Finally, we show that as in in vitro also in in vivo a short administration of diazepam promotes EGFR expression in prominin 1 stem cells causing activation and cell cycle entry. Thus, our data indicate that endogenous GABA is a part of a regulatory mechanism of size and cell cycle entry of neonatal stem cells. Our results also have potential implications for the therapeutic practices that involve exposure to GABA A Rs modulators during neurodevelopment. STEM CELLS 2011;29:307-319 Disclosure of potential conflicts of interest is found at the end of this article.

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Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors

Cited by 399 publications

References 45 publications

GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb

GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

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