%0 Journal Article
%T DLK1 Protein Expression during Mouse Development Provides New Insights into Its Function
%A F. A. Falix
%A M. R. S. Tjon-A-Loi
%A I. C. Gaemers
%A D. C. Aronson
%A W. H. Lamers
%J ISRN Developmental Biology
%D 2013
%R 10.1155/2013/628962
%X 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. 1. Introduction DLK1, also known as preadipocyte factor 1 (Pref-1), is a transmembrane EGF-like protein consisting of an N-terminal signal sequence, six EGF-like repeats, a short juxta-membrane region containing a TACE-mediated cleavage site, a transmembrane domain, and a short C-terminal cytoplasmic tail [1, 2]. DLK1 is a noncanonical member of the evolutionarily conserved Delta-Notch signalling pathway, which is involved in stem-cell decisions during development [3]. Although DLK1 lacks the Delta-Serrate-Lag2 (DSL) domain for binding with the EGF-like repeats of Notch receptors, which all canonical Notch ligands possess [4, 5], specific interaction of DLK1 with the NOTCH1 receptor was demonstrated with the yeast two-hybrid system and Notch1 signalling was inhibited by Dlk1 [6, 7]. Furthermore, in Drosophila, Dlk1 was shown to regulate the function of the Notch receptor, resulting in an altered cellular distribution of Notch itself and inhibition of expression of Notch target genes [8]. DLK1 function has been studied most in the murine preadipocyte cell line 3T3L1, which expresses both the transmembrane (55£¿kDa) and soluble (50£¿kDa) form of the DLK1 protein. Soluble DLK1 acts as an inhibitor of adipogenesis, preventing the differentiation of murine preadipocytes into mature adipocytes [1, 9, 10]. However, recent data show that DLK1 is also able to promote adipogenesis of mesenchymal stem cells [4]. Other proposed roles for DLK1 have been in maturation along the chromaffin lineage
%U http://www.hindawi.com/journals/isrn.developmental.biology/2013/628962/