Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7356
pubmed:dateCreated
2011-7-21
pubmed:abstractText
The gene for the atypical NOTCH ligand delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms that function in several developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally inherited chromosome. Here we show that mice that are deficient in Dlk1 have defects in postnatal neurogenesis in the subventricular zone: a developmental continuum that results in depletion of mature neurons in the olfactory bulb. We show that DLK1 is secreted by niche astrocytes, whereas its membrane-bound isoform is present in neural stem cells (NSCs) and is required for the inductive effect of secreted DLK1 on self-renewal. Notably, we find that there is a requirement for Dlk1 to be expressed from both maternally 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. The results emphasize molecular relationships between NSCs and the niche astrocyte cells of the microenvironment, identifying a signalling system encoded by a single gene that functions coordinately 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 in specific developmental contexts.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
475
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
381-5
pubmed:dateRevised
2011-9-29
pubmed:meshHeading
pubmed-meshheading:21776083-Aging, pubmed-meshheading:21776083-Animals, pubmed-meshheading:21776083-Animals, Newborn, pubmed-meshheading:21776083-Astrocytes, pubmed-meshheading:21776083-Base Sequence, pubmed-meshheading:21776083-Cell Membrane, pubmed-meshheading:21776083-Cells, Cultured, pubmed-meshheading:21776083-Embryo, Mammalian, pubmed-meshheading:21776083-Female, pubmed-meshheading:21776083-Genomic Imprinting, pubmed-meshheading:21776083-Genotype, pubmed-meshheading:21776083-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:21776083-Male, pubmed-meshheading:21776083-Mice, pubmed-meshheading:21776083-Mice, Inbred C57BL, pubmed-meshheading:21776083-Neural Stem Cells, pubmed-meshheading:21776083-Neurogenesis, pubmed-meshheading:21776083-Olfactory Bulb, pubmed-meshheading:21776083-Protein Isoforms, pubmed-meshheading:21776083-Stem Cell Niche
pubmed:year
2011
pubmed:articleTitle
Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis.
pubmed:affiliation
Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't