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

Sacri R. Ferrón, Marika Charalambous, Elizabeth Radford, Kirsten McEwen, Hendrik Wildner, Eleanor Hind, Jose Manuel Morante-Redolat, Jorge Laborda, Francois Guillemot, Steven R. Bauer, Isabel Fariñas and Anne C. Ferguson-Smith ()
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Sacri R. Ferrón: Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
Marika Charalambous: Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
Elizabeth Radford: Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
Kirsten McEwen: Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
Hendrik Wildner: National Institute for Medical Research, Medical Research Council, London NW7 1AA, UK
Eleanor Hind: Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK
Jose Manuel Morante-Redolat: Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Universidad de Valencia, 46100 Burjassot, Spain
Jorge Laborda: Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Avenida de Almansa 14, 02006 Albacete, Spain
Francois Guillemot: National Institute for Medical Research, Medical Research Council, London NW7 1AA, UK
Steven R. Bauer: Cellular and Tissue Therapies Branch, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
Isabel Fariñas: Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Universidad de Valencia, 46100 Burjassot, Spain
Anne C. Ferguson-Smith: Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK

Nature, 2011, vol. 475, issue 7356, 381-385

Abstract: Selective loss of imprinting in neurogenesis Life-long neurogenesis is known to occur in some areas of the mammalian adult brain, including in the subventricular zone (SVZ), where interaction between neural precursor cells and resident astrocytes can produced migratory neuroblasts. Here, Anne Ferguson-Smith and colleagues reveal a differential role for the same developmental gene, Dlk1, in neural precursor cells and astrocytes. The gene product, the Notch ligand DLK1, has two isoforms. One is an inductive niche factor secreted by astrocytes, and the other is a membrane-bound isoform required by the neural stem cells themselves to respond to secreted DLK1. Selective changes of imprinting with age modulate the role of Dlk1 in each cell type in mice, regulating neurogenesis when establishing the adult neurogenic niche. The modulation of genomic imprinting in a stem-cell environment adds a previously unrecognized element to epigenetic regulation.

Date: 2011
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DOI: 10.1038/nature10229

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