Function and evolution of the atypical Notch ligands Dlk1 and Dlk2 during vertebrate development. (360G-Wellcome-097421_Z_11_Z)

Delta-like homologue 1 (Dlk1) is a vertebrate-specific atypical Notch ligand involved in development of multiple lineages in mouse. Genetic studies have shown it to be a key regulator within several pre and postnatal stem cell niches. Murine Dlk1 encodes soluble or membrane-bound protein isoforms depending on the presence of a juxtamembrane protein cleavage site, removed inalternatively spliced transcripts. Deciphering the signaling mechanisms of Dlk1 and the different functions of the Dlk1 isoforms has been very challenging in mouse. Zebrafish (Danio rerio) is an ideal model system to elucidate the fundamental aspects of Dlk1 function due to the relative ease and availability of molecular tools and techniques. In addition, Dlk1 in zebrafish is missing the juxtamembrane motif, whereas a closely related vertebrate-specific gene Dlk2, retains it, suggesting that zebrafish may use adifferent mechanism to produce membrane-bound and soluble Dlk, fulfilled by Dlk1 and Dlk2 respectively. Such proposed gene-specific functions make zebrafish a tractable model to decipher the specific roles of the secreted and