DLK1

Версия от 18:27, 12 мая 2021; OdysseusBot (обсуждение | вклад) (Новая страница: «Protein delta homolog 1 precursor (DLK-1) (pG2) [Contains: Fetal antigen 1 (FA1)] [DLK] ==Publications== {{medline-entry |title=Dual role of delta-like 1 homolo...»)
(разн.) ← Предыдущая версия | Текущая версия (разн.) | Следующая версия → (разн.)

Protein delta homolog 1 precursor (DLK-1) (pG2) [Contains: Fetal antigen 1 (FA1)] [DLK]

PublicationsПравить

Dual role of delta-like 1 homolog (DLK1) in skeletal muscle development and adult muscle regeneration.

Muscle development and regeneration is tightly orchestrated by a specific set of myogenic transcription factors. However, factors that regulate these essential myogenic inducers remain poorly described. Here, we show that delta-like 1 homolog (Dlk1), an imprinted gene best known for its ability to inhibit adipogenesis, is a crucial regulator of the myogenic program in skeletal muscle. Dlk1(-/-) mice were developmentally retarded in their muscle mass and function owing to inhibition of the myogenic program during embryogenesis. Surprisingly however, Dlk1 depletion improves in vitro and in vivo adult skeletal muscle regeneration by substantial enhancement of the myogenic program and muscle function, possibly by means of an increased number of available myogenic precursor cells. By contrast, Dlk1 fails to alter the adipogenic commitment of muscle-derived progenitors in vitro, as well as intramuscular fat deposition during in vivo regeneration. Collectively, our results suggest a novel and surprising dual biological function of DLK1 as an enhancer of muscle development, but as an inhibitor of adult muscle regeneration.

MeSH Terms

  • Adipogenesis
  • Adiponectin
  • Aging
  • Animals
  • Calcium-Binding Proteins
  • Cell Size
  • Cells, Cultured
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Development
  • Muscle Fibers, Skeletal
  • Muscle, Skeletal
  • Organ Size
  • Phenotype
  • Regeneration

Keywords

  • Delta-like 1 homolog
  • Mouse
  • Muscle development
  • Muscle regeneration
  • Muscle stem cells


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

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.

MeSH Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Astrocytes
  • Base Sequence
  • Calcium-Binding Proteins
  • Cell Membrane
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Genomic Imprinting
  • Genotype
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells
  • Neurogenesis
  • Olfactory Bulb
  • Protein Isoforms
  • Stem Cell Niche