DLK1 genetics and its emerging role in human puberty

Abstract The existence of a direct relation between weight gain and the age of pubertal onset has been demonstrated in humans. Delta-Like 1 Homolog (DLK1) acts as an adipogenesis gatekeeper by preventing adipocyte differentiation. This transmembrane protein is a well-known non-canonical ligand of Notch signaling involved in cell state and fate. DLK1 is encoded by an imprinted gene (paternally expressed) located on the long arm of chromosome 14 (14q32.2) that is expressed in several hypothalamic nuclei as well as in kisspeptin cell lines. Notably, DLK1 locus was associated with the age of menarche in large genome wide association studies. More recently, several DLK1 loss-of-function mutations were identified in children with familial central precocious puberty as well as in women who presented very early menarche (