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.
Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Winsloewparken 21 3rd, 5000 Odense C, Denmark.
Ditte Caroline
DC
Andersen
Jorge
J
Laborda
Victoriano
V
Baladron
Moustapha
M
Kassem
Søren Paludan
SP
Sheikh
Charlotte Harken
CH
Jensen
D050156:Adipogenesis; D052242:Adiponectin / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins; D048429:Cell Size; D002478:Cells, Cultured; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009929:Organ Size; D010641:Phenotype; D012038:Regeneration / Q000502:physiology*
D052242:Adiponectin; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins
Delta-like 1 homolog; Mouse; Muscle development; Muscle regeneration; Muscle stem cells