Stable expression of the tyrosine kinase receptor ErbB4 confers increased migratory behavior to the neural progenitor cell line ST14A. We used microarray analysis to identify transcriptional changes associated with higher migratory activity mediated by specific ErbB4 isoforms, and found up-regulation of Eps8, a multimodular regulator of actin dynamics. Using transwell assays and experimental manipulation of Eps8 expression levels, we show that Eps8 synergizes with ErbB4 to confer increased migratory capability to ST14A cells, whereas siRNA mediated Eps8 silencing impaired both basal and neuregulin1 (NRG1) stimulated migration. In vivo, ErbB4 is involved in regulating the migratory behavior of olfactory bulb neuronal precursors. We observed that newly generated neurons, which migrate from the subventricular zone (SVZ) towards the olfactory bulb (OB) through the rostral migratory stream (RMS), express high levels of Eps8. We thus tested in this model system whether down-regulation of Eps8 would affect neuronal precursor migration. Using transient knockdown of Eps8 by in vivo siRNA electroporation, followed by primary cultures of SVZ explants, we demonstrate that this is indeed the case. In line with the results obtained in ST14A cells, Eps8 down-regulation inhibited migration of olfactory bulb precursors. In conclusion, our data demonstrate that Eps8 is a key regulator of neuronal progenitor motility both in basal conditions and in response to external motogenic cues. This work was supported by grants from the Ministero Italiano della Università e della Ricerca (PRIN 2007) Regione Piemonte (Bando Ricerca Sanitaria Finalizzata), Università di Torino.
The down-regulation of Eps8 inhibits migration of ErbB4-expressing ST14A cells and olfactory bulb neuronal precursors
FREGNAN, Federica;GARZOTTO, Donatella;GNAVI, SARA;DE MARCHIS, Silvia;PERROTEAU, Isabelle;GAMBAROTTA, Giovanna
2010-01-01
Abstract
Stable expression of the tyrosine kinase receptor ErbB4 confers increased migratory behavior to the neural progenitor cell line ST14A. We used microarray analysis to identify transcriptional changes associated with higher migratory activity mediated by specific ErbB4 isoforms, and found up-regulation of Eps8, a multimodular regulator of actin dynamics. Using transwell assays and experimental manipulation of Eps8 expression levels, we show that Eps8 synergizes with ErbB4 to confer increased migratory capability to ST14A cells, whereas siRNA mediated Eps8 silencing impaired both basal and neuregulin1 (NRG1) stimulated migration. In vivo, ErbB4 is involved in regulating the migratory behavior of olfactory bulb neuronal precursors. We observed that newly generated neurons, which migrate from the subventricular zone (SVZ) towards the olfactory bulb (OB) through the rostral migratory stream (RMS), express high levels of Eps8. We thus tested in this model system whether down-regulation of Eps8 would affect neuronal precursor migration. Using transient knockdown of Eps8 by in vivo siRNA electroporation, followed by primary cultures of SVZ explants, we demonstrate that this is indeed the case. In line with the results obtained in ST14A cells, Eps8 down-regulation inhibited migration of olfactory bulb precursors. In conclusion, our data demonstrate that Eps8 is a key regulator of neuronal progenitor motility both in basal conditions and in response to external motogenic cues. This work was supported by grants from the Ministero Italiano della Università e della Ricerca (PRIN 2007) Regione Piemonte (Bando Ricerca Sanitaria Finalizzata), Università di Torino.
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