dc.contributor.author	Singh, Shalini
dc.contributor.author	Howell, Danielle
dc.contributor.author	Trivedi, Niraj
dc.contributor.author	Kessler, Ketty
dc.contributor.author	Ong, Taren
dc.contributor.author	Rosmaninho, Pedro
dc.contributor.author	Raposo, Alexandre ASF
dc.contributor.author	Robinson, Giles
dc.contributor.author	Roussel, Martine F
dc.contributor.author	Castro, Diogo S
dc.contributor.author	Solecki, David J
dc.date.accessioned	2017-03-06T16:20:11Z
dc.date.available	2017-03-06T16:20:11Z
dc.date.issued	2016-05-14
dc.description.abstract	In the developing mammalian brain, differentiating neurons mature morphologically via neuronal polarity programs. Despite discovery of polarity pathways acting concurrently with differentiation, it's unclear how neurons traverse complex polarity transitions or how neuronal progenitors delay polarization during development. We report that zinc finger and homeobox transcription factor-1 (Zeb1), a master regulator of epithelial polarity, controls neuronal differentiation by transcriptionally repressing polarity genes in neuronal progenitors. Necessity-sufficiency testing and functional target screening in cerebellar granule neuron progenitors (GNPs) reveal that Zeb1 inhibits polarization and retains progenitors in their germinal zone (GZ). Zeb1 expression is elevated in the Sonic Hedgehog (SHH) medulloblastoma subgroup originating from GNPs with persistent SHH activation. Restored polarity signaling promotes differentiation and rescues GZ exit, suggesting a model for future differentiative therapies. These results reveal unexpected parallels between neuronal differentiation and mesenchymal-to-epithelial transition and suggest that active polarity inhibition contributes to altered GZ exit in pediatric brain cancers.	pt_PT
dc.description.sponsorship	National Institute of Neurological Disorders and Stroke grant: (1R01NS066936); March of Dimes Foundation grant: (#1-FY12-455).	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	eLife 2016;5:e12717	pt_PT
dc.identifier.doi	10.7554/eLife.12717	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/738
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	eLife Sciences Publications	pt_PT
dc.relation.publisherversion	https://elifesciences.org/content/5/e12717/article-metrics	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	Development Biology	pt_PT
dc.subject	Stem Cells	pt_PT
dc.subject	Neuroscience	pt_PT
dc.subject	cell adhesion	pt_PT
dc.subject	mesenchymal-epithelial transition	pt_PT
dc.subject	Mouse	pt_PT
dc.subject	neuronal differentition	pt_PT
dc.subject	neuronal migration	pt_PT
dc.subject	neuronal polarity	pt_PT
dc.subject	PAR polarity complex	pt_PT
dc.title	Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal-epithelial-like transition	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.endPage	31	pt_PT
oaire.citation.startPage	1	pt_PT
oaire.citation.title	eLife	pt_PT
oaire.citation.volume	5	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT

Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal-epithelial-like transition

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