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Postnatal loss of Dlk1 imprinting in stem cells and niche-astrocytes regulates neurogenesis

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Postnatal loss of Dlk1 imprinting in stem cells and niche-astrocytes regulates neurogenesis

dc.contributor.author	Ferrón, Sacri R.	es_ES
dc.contributor.author	Charalambous, Marika	es_ES
dc.contributor.author	Radford, Elizabeth	es_ES
dc.contributor.author	McEwen, Kirsten	es_ES
dc.contributor.author	Wildner, Hendrik	es_ES
dc.contributor.author	Hind, Eleanor	es_ES
dc.contributor.author	Morante Redolat, Jose Manuel	es_ES
dc.contributor.author	Laborda, Jorge	es_ES
dc.contributor.author	Guillemot, Francois	es_ES
dc.contributor.author	Bauer, Steven R.	es_ES
dc.contributor.author	Fariñas Gómez, Isabel	es_ES
dc.contributor.author	Ferguson-Smith, Anne C	es_ES
dc.date.accessioned	2015-06-22T09:51:17Z
dc.date.available	2015-06-22T09:51:17Z
dc.date.issued	2011	es_ES
dc.identifier.citation	Nature Vol. 475 Issue 7356: pp. 381-385	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44676
dc.description.abstract	The gene for the atypical Notch ligand Delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms functioning in multiple developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally-inherited chromosome1,2. Here we show that mice deficient in Dlk1 exhibit defects in postnatal neurogenesis within the subventricular zone (SVZ), a developmental continuum resulting in depletion of mature neurons in the olfactory bulb. We show that DLK1 is a factor secreted by niche-astrocytes, while its membrane-bound isoform is present in neural stem cells (NSCs) being required for the inductive effect of secreted DLK1 on self-renewal. Surprisingly, we find a requirement for Dlk1 expressed from both maternal and paternally inherited chromosomes. Selective absence of Dlk1 imprinting in both NSCs and niche astrocytes is associated with postnatal acquisition of DNA methylation at the germ line-derived imprinting control region (IG-DMR). The results emphasize molecular relationships between NSCs and niche-astrocytes identifying a signalling system coded by a single gene functioning co-ordinately in both cell types. The modulation of genomic imprinting in a stem cell environment adds a new level of epigenetic regulation to the establishment and maintenance of the niche raising wider questions about the adaptability, function, and evolution of imprinting within specific developmental contexts.	es_ES
dc.title	Postnatal loss of Dlk1 imprinting in stem cells and niche-astrocytes regulates neurogenesis	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1038/nature10229	es_ES
dc.identifier.idgrec	075920	es_ES