title: Two deltaC splice-variants have distinct signaling abilities during somitogenesis and midline patterning.
abstract: Notch signaling is required for many developmental processes, yet differences in the signaling abilities of various Notch ligands are poorly understood. Here, we have isolated a splice variant of the zebrafish Notch ligand deltaC in which the inclusion of the last intron leads to a truncation of the C-terminal 39 amino acids (deltaC(tv2)). We show that, unlike deltaC(tv1), deltaC(tv2) cannot function effectively in somitogenesis but has an enhanced ability to signal during midline development. Additionally, over-expression of deltaC(tv2) preferentially affects anterior midline development, while another Notch ligand, deltaD, shows a posterior bias. Using chimeric Deltas we show that the intracellular domain is responsible for the strength of signal in midline development, while the extracellular domain influences the anterior-posterior bias of the effect. Together our data show that different deltas can signal in biologically distinct ways in both midline formation and somitogenesis. Moreover, it illustrates the importance of cell-type-dependent modifiers of Notch signaling in providing ligand specificity.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, CT 06520, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mara
authors.forename: Joshua
authors.initials: J
authors.lastname: Schroeder
authors.forename: Scott A
authors.initials: SA
authors.lastname: Holley
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D019170:Somites / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D029961:Zebrafish Proteins; C064045:delta protein