Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR

Ciccolini, Francesca; Mandl, Claudia; Hölzl‐Wenig, Gabriele; Kehlenbach, Angelika; Hellwig, Andrea

doi:10.1016/j.ydbio.2005.05.007

Cited by 72 publications

(98 citation statements)

References 45 publications

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“…Our findings on the role of EGFR signaling in SVZ cell migration are consistent with previous studies (Caric et al, 2001;Ciccolini et al, 2005), including our own showing that overexpression of EGFR induced a migratory phenotype in non-migratory cortical NG2+ both in vitro and in vivo after transplantation (Aguirre et al, 2005). These results have been confirmed in an independent study, in which an EGFR-GFP fusion protein was constitutively expressed in white matter glial progenitors.…”

Section: Discussionsupporting

confidence: 93%

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

Aguirre

Gallo

2007

Neuron Glia Biol.

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Neural progenitor cells expressing the NG2 proteoglycan are found in different regions of the adult mammalian brain, where they display distinct morphologies and proliferative rates. In the developing postnatal and adult mouse, NG2 + cells represent a major cell population of the subventricular zone (SVZ). NG2 + cells divide in the anterior and lateral region of the SVZ, and are stimulated to proliferate and migrate out of the SVZ by focal demyelination of the corpus callosum (CC). Many NG2 + cells are labeled by GFP-retrovirus injection into the adult SVZ, demonstrating that NG2 + cells actively proliferate under physiological conditions and after demyelination. In the wa2 mouse, which is characterized by reduced EGFR signaling, NG2 + cell proliferation, under normal physiological conditions and after focal demyelination, is significantly attenuated. This results in reduced SVZ-to-lesion migration of NG2 + cells and oligodendrogenesis in the lesion. Expression of VEGF and EGFR ligands, such as HB-EGF and TGF-alpha, is upregulated in the SVZ after focal demyelination of the CC. EGF-induced oligodendrogenesis and myelin protein expression in cultured wild-type SVZ cells were significantly attenuated in wa2 SVZ cells. Our results demonstrate that the NG2 + cell response in the SVZ and their subsequent differentiation in CC after focal demyelination are dependent upon EGFR signaling.

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Section: Discussionsupporting

confidence: 93%

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

Aguirre

Gallo

2007

Neuron Glia Biol.

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“…For clonal analysis, single cells were plated by FACS-automated cell deposition in each well of 96-well plates (Nunc, Wiesbaden, Germany) in NSA proliferation medium as described before [13]. Changes in forward scattering (FSC) reflected variations in the osmolarity of the medium (Supporting Information Fig.…”

Section: Facs and Clonal Analysismentioning

confidence: 99%

“…Slices were cultured as described previously [13]. Slices were infected by pipetting 1 ll viral dilution onto the lateral ventricle and analyzed 2 days later.…”

Section: Organotypic Slice Preparation and Infectionmentioning

confidence: 99%

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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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“…For live immunostaining, cells were first incubated with primary PSANCAM, LeX/SSEA1, or NG2 antibodies and secondary antibodies conjugated to fluorescent fluorophores (Molecular Probes Inc.) and then processed for EGF-A staining as previously described [21].…”

Section: Fluorescence-activated Cell Sorting and Clonal Analysismentioning

confidence: 99%

Analysis of Stem Cell Lineage Progression in the Neonatal Subventricular Zone Identifies EGFR+/NG2− Cells as Transit-Amplifying Precursors

Cesetti¹,

Obernier²,

Bengtson³

et al. 2009

Stem Cells

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In the adult subventricular zone (SVZ), astroglial stem cells generate transit-amplifying precursors (TAPs). Both stem cells and TAPs form clones in response to epidermal growth factor (EGF). However, in vivo, in the absence of sustained EGF receptor (EGFR) activation, TAPs divide a few times before differentiating into neuroblasts. The lack of suitable markers has hampered the analysis of stem cell lineage progression and associated functional changes in the neonatal germinal epithelium. Here we purified neuroblasts and clone-forming precursors from the neonatal SVZ using expression levels of EGFR and polysialylated neural cell adhesion molecule (PSANCAM). As in the adult SVZ, most neonatal clone-forming precursors did not express the neuroglia proteoglycan 2 (NG2) but displayed characteristics of TAPs, and only a subset exhibited antigenic characteristics of astroglial stem cells. Both precursors and neuroblasts were PSANCAM 1 ; however, neuroblasts also expressed doublecortin and functional voltage-dependent Ca 21 channels. Neuroblasts and precursors had distinct outwardly rectifying K 1 current densities and passive membrane properties, particularly in precursors contacting each other, because of the contribution of gap junction coupling. Confirming the hypothesis that most are TAPs, cell tracing in brain slices revealed that within 2 days the majority of EGFR 1 cells had exited the cell cycle and differentiated into a progenitor displaying intermediate antigenic and functional properties between TAPs and neuroblasts. Thus, distinct functional and antigenic properties mark stem cell lineage progression in the neonatal SVZ.

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Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR

Cited by 72 publications

References 45 publications

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

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

Analysis of Stem Cell Lineage Progression in the Neonatal Subventricular Zone Identifies EGFR+/NG2− Cells as Transit-Amplifying Precursors

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