DLK1 Protein Expression during Mouse Development Provides New Insights into Its Function

Abstract

Delta-like 1 homolog (DLK1) is a noncanonical ligand in the Delta-Notch signalling pathway. Although Dlk1 mRNA is abundantly present embryonically and declines rapidly just before birth, Dlk1 knockouts display a relatively mild phenotype. To assess whether this mild phenotype was due to posttranscriptional regulation, we studied the expression of DLK1 protein in mouse embryos and found abundant expression in liver, lung, muscle, vertebrae, pancreas, pituitary, and adrenal gland(s). DLK1 expression was absent in heart, stomach, intestine, kidney, epidermis, and central nervous system. DLK1 protein expression, therefore, correlates well with the reported Dlk1 mRNA expression pattern, which shows that its expression is mainly regulated at the pretranslational level. The comparison of the reported expression patterns of Notch mRNA and those of DLK1 in organs where lineage commitment and branching morphogenesis are important developmental processes suggests that DLK1 is a ligand that prevents premature Notch-dependent differentiation, possibly by competing with canonical ligands.