Involvement of β1-Integrin Up-regulation in Basic Fibroblast Growth Factor- and Epidermal Growth Factor-induced Proliferation of Mouse Neuroepithelial Cells

Suzuki, Yusuke; Yanagisawa, Makoto; Yagi, Hirokazu; Nakatani, Yoshihiko; Yu, Robert K.

doi:10.1074/jbc.m110.114645

Cited by 28 publications

(27 citation statements)

References 70 publications

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“…Previous studies demonstrated that cooperativity between the integrin and EGFR signaling pathways plays a crucial role in maintaining the embryonic neocortical stem cell niche and regulating both the NSC number and the ability of self-renewal (16,17). To test the association of GD3 with integrin and EGFR, we measured the expression levels of EGFR and β1-integrin in neurospheres from GD3S +/+ and GD3S −/− mouse brains.…”

Section: Resultsmentioning

confidence: 99%

Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

Wang

2013

Proc. Natl. Acad. Sci. U.S.A.

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102

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Mounting evidence supports the notion that gangliosides serve regulatory roles in neurogenesis; little is known, however, about how these glycosphingolipids function in neural stem cell (NSC) fate determination. We previously demonstrated that ganglioside GD3 is a major species in embryonic mouse brain: more than 80% of the NSCs obtained by the neurosphere method express GD3. To investigate the functional role of GD3 in neurogenesis, we compared the properties of NSCs from GD3-synthase knockout (GD3S-KO) mice with those from their wild-type littermates. NSCs from GD3S-KO mice showed decreased self-renewal ability compared with those from the wild-type animals, and that decreased ability was accompanied by reduced expression of EGF receptor (EGFR) and an increased degradation rate of EGFR and EGF-induced ERK signaling. We also showed that EGFR switched from the low-density lipid raft fractions in wild-type NSCs to the high-density layers in the GD3S-KO NSCs. Immunochemical staining revealed colocalization of EGFR and GD3, and EGFR could be immunoprecipitated from the NSC lysate with an anti-GD3 antibody from the wild-type, but not from the GD3S-KO, mice. Tracking the localization of endocytosed EGFR with endocytosis pathway markers indicated that more EGFR in GD3S-KO NSCs translocated through the endosomal−lysosomal degradative pathway, rather than through the recycling pathway. Those findings support the idea that GD3 interacts with EGFR in the NSCs and that the interaction is responsible for sustaining the expression of EGFR and its downstream signaling to maintain the selfrenewal capability of NSCs.G angliosides are ubiquitously expressed in all vertebrate cells and are particularly abundant in the nervous system (1). In early mammalian embryonic brain, the pattern of ganglioside expression is limited to simple gangliosides, predominantly GM3 (NeuAcα2-3Galβ1-4Glcβ1-1′Cer) and GD3 (NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1′Cer). In later developmental stages, however, more complex gangliosides prevail, particularly GM1 (Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glcβ1-1′Cer), GD1a (NeuAcα2-3Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glcβ1-1′ Cer), GD1b (Galβ1-3GalNAcβ1-4(NeuAcα2-8NeuAcα2-3) Galβ1-4Glcβ1-1′Cer), and GT1b (NeuAcα2-3Galβ1-3GalNAcβ1-4 (NeuAcα2-8NeuAcα2-3)Galβ1-4Glcβ1-1′Cer) (2, 3). Because of the spatiotemporal expression patterns, gangliosides abundant in embryonic brain, such as GD3 and the c-series ganglioside antigen marker A2B5, have been considered to be useful stage-specific markers of early brain development (4, 5). Mounting evidence supports the notion that gangliosides serve regulatory roles in neurogenesis through modulating processes, such as intercellular recognition, interaction, adhesion, reception, and/ or signaling (6-9). Little is known, however, about how glycosphingolipids (GSLs) function in neural stem cell (NSC) fate determination. Investigation of the biological significance of gangliosides has also been greatly facilitated by the analysis of genetically engineered mice deficient in one or more gangl...

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Section: Resultsmentioning

confidence: 99%

Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

Wang

2013

Proc. Natl. Acad. Sci. U.S.A.

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102

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“…However, Notch signaling is unlikely to be involved, because it occurs between sibling cells that contact each other via short processes rather than the basal process. Interestingly, the self-renewal of ferret OSVZ progenitor cells depends on integrin function (Fietz et al, 2010), which coordinately regulates cell proliferation with growth factor signaling pathways in neural stem cells (Campos et al, 2006;Suzuki et al, 2010). Thus, the basal process may be involved in cell proliferation independent of Notch signaling, thereby contributing to progenitor self-renewal.…”

Section: Discussionmentioning

confidence: 99%

Oblique Radial Glial Divisions in the Developing Mouse Neocortex Induce Self-Renewing Progenitors outside the Germinal Zone That Resemble Primate Outer Subventricular Zone Progenitors

Shitamukai¹,

Konno²,

Matsuzaki³

2011

J. Neurosci.

412

548

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Radial glia cells function as neural stem cells in the developing brain and generate self-renewing and differentiating daughter cells by asymmetric cell divisions. During these divisions, the apical process or basal process of the elongated epithelial structure is asymmetrically partitioned into daughter cells, depending on developmental contexts. However, in mammalian neurogenesis, the relationship between these subcellular structures and self-renewability is largely unknown. We induced oblique cleavages of radial glia cells to split the apical and basal processes into two daughters, and investigated the fate and morphology of the daughters in slice cultures. We observed that the more basal daughter cell that inherits the basal process self-renews outside of the ventricular zone (VZ), while the more apical daughter cell differentiates. These self-renewing progenitors, termed "outer VZ progenitors," retain the basal but not the apical process, as recently reported for the outer subventricular zone (OSVZ) progenitors in primates (Fietz et al., 2010; Hansen et al., 2010); to selfrenew, they require clonal Notch signaling between sibling cells. We also found a small endogenous population of outer VZ progenitors in the mouse embryonic neocortex, consistent with a low frequency of oblique radial glia divisions. Our results describe the general role of the basal process in the self-renewal of neural progenitors and implicate the loss of the apical junctions during oblique divisions as a possible mechanism for generating OSVZ progenitors. We propose that mouse outer VZ progenitors, induced by oblique cleavages, provide a model to study both progenitor self-renewal and OSVZ progenitors.

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“…The spectrophotometric absorbance measured by this assay is highly correlative with the number of living cells. TUNEL Assay-Apoptotic cells were detected with the TUNEL (terminal deoxynucleotididyl transferase-mediated dUTP nick-end labeling) assay (34,35). In brief, the siRNAtransfected cells were plated onto chamber slides and cultured for 3 days.…”

Section: Identification Of Glycoproteins By Lc-ms/ms Analysis-for Liqmentioning

confidence: 99%

HNK-1 Epitope-carrying Tenascin-C Spliced Variant Regulates the Proliferation of Mouse Embryonic Neural Stem Cells

Yagi

Yanagisawa

Suzuki

et al. 2010

Journal of Biological Chemistry

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Neural stem cells (NSCs) possess high proliferative potential and the capacity for self-renewal with retention of multipotency to differentiate into neuronal and glial cells. NSCs are the source for neurogenesis during central nervous system development from fetal and adult stages. Although the human natural killer-1 (HNK-1) carbohydrate epitope is expressed predominantly in the nervous system and involved in intercellular adhesion, cell migration, and synaptic plasticity, the expression patterns and functional roles of HNK-1-containing glycoconjugates in NSCs have not been fully recognized. We found that HNK-1 was expressed in embryonic mouse NSCs and that this expression was lost during the process of differentiation. Based on proteomics analysis, it was revealed that the HNK-1 epitopes were almost exclusively displayed on an extracellular matrix protein, tenascin-C (TNC), in the mouse embryonic NSCs. Furthermore, the HNK-1 epitope was found to be present only on the largest isoform of the TNC molecules. In addition, the expression of HNK-1 was dependent on expression of the largest TNC variant but not by enzymes involved in the biosynthesis of HNK-1. By knocking down HNK-1 sulfotransferase or TNC by small interfering RNA, we further demonstrated that HNK-1 on TNC was involved in the proliferation of NSCs via modulation of the expression level of the epidermal growth factor receptor. Our finding provides insights into the function of HNK-1 carbohydrate epitopes in NSCs to maintain stemness during neural development. Neural stem cells (NSCs)4 are undifferentiated neural cells characterized by their high proliferative potential and the capacity for self-renewal with retention of multipotency to differentiate into brain-forming cells, such as neurons, astrocytes, and oligodendrocytes (1-3). Environmental factors of NSCs, such as various growth factors, the extracellular matrix (ECM), and cell adhesion molecules, are known to play important roles in the maintenance of the stem cell population throughout specific cell lineage pathways (4 -7).Glycoconjugates, including glycoproteins, proteoglycans, and glycolipids, are expressed mainly on the cell surface as ECM, and they are known to regulate cell-to-cell communications. Certain glycoconjugates also serve as excellent biomarkers at various stages of the cellular differentiation of NSCs and play important functional roles in determining cell fate (8 -12). For example, stage-specific embryonic antigen-1 (SSEA-1), which is well known as a specific maker of undifferentiated cells including mouse embryonic stem cells, is expressed on NSCs and associated with cell migration (8, 10, 13). Recently, we have also demonstrated that cells positive for GD3 ganglioside (NeuAc␣2-8NeuAc␣2-3Gal␤1-4Glc␤1-1ЈCer) isolated from mouse brains of various ages possess characteristics of neural stem cells (11).The human natural killer-1 (HNK-1) carbohydrate epitope (CD57) was originally reported as a specific antigenic determinant for human natural killer cells (14) but is now widely known ...

show abstract

Involvement of β1-Integrin Up-regulation in Basic Fibroblast Growth Factor- and Epidermal Growth Factor-induced Proliferation of Mouse Neuroepithelial Cells

Cited by 28 publications

References 70 publications

Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

Oblique Radial Glial Divisions in the Developing Mouse Neocortex Induce Self-Renewing Progenitors outside the Germinal Zone That Resemble Primate Outer Subventricular Zone Progenitors

HNK-1 Epitope-carrying Tenascin-C Spliced Variant Regulates the Proliferation of Mouse Embryonic Neural Stem Cells

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