ERK-dependent and -independent pathways trigger human neural progenitor cell migration
Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural m...
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description | Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways. |
doi_str_mv | 10.1016/j.taap.2007.02.018 |
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For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2007.02.018</identifier><identifier>PMID: 17445854</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ACETATES ; APOPTOSIS ; Astrocytes - cytology ; Astrocytes - drug effects ; Astrocytes - metabolism ; Biological and medical sciences ; Blotting, Western ; BRAIN ; Cell Differentiation - drug effects ; Cell Movement - drug effects ; Cell Movement - physiology ; Cell Survival - drug effects ; Cells, Cultured ; EGFR ; ERK1/2 ; ETHANOL ; Flavonoids - pharmacology ; GENE REGULATION ; GROWTH FACTORS ; HUMAN POPULATIONS ; Humans ; Indoles - pharmacology ; Maleimides - pharmacology ; Medical sciences ; Methylmercury Compounds - pharmacology ; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors ; Mitogen-Activated Protein Kinase 3 - metabolism ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Neural migration ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Normal human neural progenitor cells ; PHOSPHORYLATION ; Phosphorylation - drug effects ; PHOSPHOTRANSFERASES ; PKC ; Protein Kinase C - antagonists & inhibitors ; Protein Kinase C - metabolism ; Pyrimidines - pharmacology ; Quinazolines ; RECEPTORS ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Spheroids, Cellular - cytology ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - metabolism ; src ; src-Family Kinases - antagonists & inhibitors ; src-Family Kinases - metabolism ; Stem Cells - cytology ; Stem Cells - drug effects ; Stem Cells - metabolism ; Sulfonamides - pharmacology ; Tetradecanoylphorbol Acetate - pharmacology ; Toxicology ; Tyrphostins - pharmacology</subject><ispartof>Toxicology and applied pharmacology, 2007-05, Vol.221 (1), p.57-67</ispartof><rights>2007 Elsevier Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-6a6053639dba8198985d969542e7df57fe8f5eb50dc36f2ab5ad0b334f4ef18e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2007.02.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18787567$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17445854$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/20976934$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Moors, Michaela</creatorcontrib><creatorcontrib>Cline, Jason E.</creatorcontrib><creatorcontrib>Abel, Josef</creatorcontrib><creatorcontrib>Fritsche, Ellen</creatorcontrib><title>ERK-dependent and -independent pathways trigger human neural progenitor cell migration</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ACETATES</subject><subject>APOPTOSIS</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>BRAIN</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Movement - drug effects</subject><subject>Cell Movement - physiology</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>EGFR</subject><subject>ERK1/2</subject><subject>ETHANOL</subject><subject>Flavonoids - pharmacology</subject><subject>GENE REGULATION</subject><subject>GROWTH FACTORS</subject><subject>HUMAN POPULATIONS</subject><subject>Humans</subject><subject>Indoles - pharmacology</subject><subject>Maleimides - pharmacology</subject><subject>Medical sciences</subject><subject>Methylmercury Compounds - pharmacology</subject><subject>Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Neural migration</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Normal human neural progenitor cells</subject><subject>PHOSPHORYLATION</subject><subject>Phosphorylation - drug effects</subject><subject>PHOSPHOTRANSFERASES</subject><subject>PKC</subject><subject>Protein Kinase C - antagonists & inhibitors</subject><subject>Protein Kinase C - metabolism</subject><subject>Pyrimidines - pharmacology</subject><subject>Quinazolines</subject><subject>RECEPTORS</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Spheroids, Cellular - cytology</subject><subject>Spheroids, Cellular - drug effects</subject><subject>Spheroids, Cellular - metabolism</subject><subject>src</subject><subject>src-Family Kinases - antagonists & inhibitors</subject><subject>src-Family Kinases - metabolism</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Sulfonamides - pharmacology</subject><subject>Tetradecanoylphorbol Acetate - pharmacology</subject><subject>Toxicology</subject><subject>Tyrphostins - pharmacology</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kNGK1DAUhoMo7uzoC3ghBdG71pMmaRPwZlnWVVwQRMW7kCanMxnadExSZd_elhmYO68OHL7_8J-PkFcUKgq0eX-osjHHqgZoK6groPIJ2VBQTQmMsadkA8BpCSB_XZHrlA4AoDinz8kVbTkXUvAN-Xn37Uvp8IjBYciFCa4ofbgsjibv_5rHVOTodzuMxX4eTSgCztEMxTFOOww-T7GwOAzF6HfRZD-FF-RZb4aEL89zS358vPt--6l8-Hr_-fbmobScs1w2pgHBGqZcZyRVUknhVKMEr7F1vWh7lL3AToCzrOlr0wnjoGOM9xx7KpFtyZvT3Sllr5P1Ge3eTiGgzboG1TaK8YV6d6KWvr9nTFmPPq2FTcBpTpqqpmWCywWsT6CNU0oRe32MfjTxUVPQq3N90KtzvTrXUOvF-RJ6fb4-dyO6S-QseQHengGTrBn6aIL16cLJVrZiabAlH04cLsb-eIzrQxgsOh_Xf9zk_9fjH8zgn_A</recordid><startdate>20070515</startdate><enddate>20070515</enddate><creator>Moors, Michaela</creator><creator>Cline, Jason E.</creator><creator>Abel, Josef</creator><creator>Fritsche, Ellen</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>OTOTI</scope></search><sort><creationdate>20070515</creationdate><title>ERK-dependent and -independent pathways trigger human neural progenitor cell migration</title><author>Moors, Michaela ; Cline, Jason E. ; Abel, Josef ; Fritsche, Ellen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-6a6053639dba8198985d969542e7df57fe8f5eb50dc36f2ab5ad0b334f4ef18e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ACETATES</topic><topic>APOPTOSIS</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>BRAIN</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Movement - drug effects</topic><topic>Cell Movement - physiology</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>EGFR</topic><topic>ERK1/2</topic><topic>ETHANOL</topic><topic>Flavonoids - pharmacology</topic><topic>GENE REGULATION</topic><topic>GROWTH FACTORS</topic><topic>HUMAN POPULATIONS</topic><topic>Humans</topic><topic>Indoles - pharmacology</topic><topic>Maleimides - pharmacology</topic><topic>Medical sciences</topic><topic>Methylmercury Compounds - pharmacology</topic><topic>Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Neural migration</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Normal human neural progenitor cells</topic><topic>PHOSPHORYLATION</topic><topic>Phosphorylation - drug effects</topic><topic>PHOSPHOTRANSFERASES</topic><topic>PKC</topic><topic>Protein Kinase C - antagonists & inhibitors</topic><topic>Protein Kinase C - metabolism</topic><topic>Pyrimidines - pharmacology</topic><topic>Quinazolines</topic><topic>RECEPTORS</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Spheroids, Cellular - cytology</topic><topic>Spheroids, Cellular - drug effects</topic><topic>Spheroids, Cellular - metabolism</topic><topic>src</topic><topic>src-Family Kinases - antagonists & inhibitors</topic><topic>src-Family Kinases - metabolism</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Stem Cells - metabolism</topic><topic>Sulfonamides - pharmacology</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><topic>Toxicology</topic><topic>Tyrphostins - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moors, Michaela</creatorcontrib><creatorcontrib>Cline, Jason E.</creatorcontrib><creatorcontrib>Abel, Josef</creatorcontrib><creatorcontrib>Fritsche, Ellen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moors, Michaela</au><au>Cline, Jason E.</au><au>Abel, Josef</au><au>Fritsche, Ellen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ERK-dependent and -independent pathways trigger human neural progenitor cell migration</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2007-05-15</date><risdate>2007</risdate><volume>221</volume><issue>1</issue><spage>57</spage><epage>67</epage><pages>57-67</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>17445854</pmid><doi>10.1016/j.taap.2007.02.018</doi><tpages>11</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES ACETATES APOPTOSIS Astrocytes - cytology Astrocytes - drug effects Astrocytes - metabolism Biological and medical sciences Blotting, Western BRAIN Cell Differentiation - drug effects Cell Movement - drug effects Cell Movement - physiology Cell Survival - drug effects Cells, Cultured EGFR ERK1/2 ETHANOL Flavonoids - pharmacology GENE REGULATION GROWTH FACTORS HUMAN POPULATIONS Humans Indoles - pharmacology Maleimides - pharmacology Medical sciences Methylmercury Compounds - pharmacology Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors Mitogen-Activated Protein Kinase 3 - metabolism Mitogen-Activated Protein Kinases - antagonists & inhibitors Neural migration Neurons - cytology Neurons - drug effects Neurons - metabolism Normal human neural progenitor cells PHOSPHORYLATION Phosphorylation - drug effects PHOSPHOTRANSFERASES PKC Protein Kinase C - antagonists & inhibitors Protein Kinase C - metabolism Pyrimidines - pharmacology Quinazolines RECEPTORS Signal Transduction - drug effects Signal Transduction - physiology Spheroids, Cellular - cytology Spheroids, Cellular - drug effects Spheroids, Cellular - metabolism src src-Family Kinases - antagonists & inhibitors src-Family Kinases - metabolism Stem Cells - cytology Stem Cells - drug effects Stem Cells - metabolism Sulfonamides - pharmacology Tetradecanoylphorbol Acetate - pharmacology Toxicology Tyrphostins - pharmacology |
title | ERK-dependent and -independent pathways trigger human neural progenitor cell migration |
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