Genomic imprinting and the epigenetic regulation of adult neurogenesis

• Autorzy: Ferron S. , Kleine I. , Ferguson-Smith A. C.
• Języki publikacji: EN

Abstrakty

EN

Genomic imprinting is a normal process causing genes to be expressed from only one of the two parental chromosome homologues according to their parental origin. Imprinted genes function in a range of developmental processes. In recent years, data has emerged indicating discordance of imprinting between mouse and man, polymorphic imprinting between different individuals and tissue-specific imprinting within individuals. This suggests that imprinting might be an adaptable and dynamic process with the potential to act as a mechanism regulating gene dosage in different developmental contexts. Delta-like homologue 1 (Dlk1) is a paternally expressed imprinted gene that encodes both a transmembrane protein and a secreted isoform generated by alternative splicing, and is an atypical member of the Notch/Delta/Serrate family of developmental signalling molecules. Although widely expressed during embryonic development, only a few tissues including neurogenic regions of the brain retain Dlk1 expression in adults. Analysis of neurogenesis in the SVZ of Dlk1 mutant mice shows a reduction in the numbers of stem cells in vivo and an impairment of newborn neurons incorporated into the olfactory bulb as well as fewer primary neurospheres in vitro suggesting that normal levels of Dlk1 are necessary for the life-long maintenance of neural stem cells (NSCs). Within the SVZ, DLK1 is a niche factor secreted by astrocytes and that membrane-bound DLK1 is required in NSCs to respond to it. In contrast to the neighbouring Gtl2 gene, we observe specific absence of Dlk1 imprinting in the stem cell and astrocyte populations in the SVZ niche indicating that the mechanism conferring biallelic expression can override the imprint selectively at Dlk1 to control normal neurogenesis in the adult brain. This neurogenic requirement for both the maternally and paternally expressed alleles of the canonically imprinted Dlk1 gene supports the hypothesis that control of gene dosage by absence of imprinting is an important developmental process. We are testing the hypothesis that other imprinted genes important in neurogenesis may also modulate imprinting to control gene dosage.

Słowa kluczowe

EN

genomics; imprinting; epigenetic regulation; adult; neurogenesis; gene expression; parental chromosome; development process; gene

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.180

Twórcy

autor

Ferron S.

• Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge, U.K.

autor

Kleine I.

• Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge, U.K.

autor

Ferguson-Smith A. C.

• Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge, U.K.