title: Spatiotemporal oscillations of Notch1, Dll1 and NICD are coordinated across the mouse PSM.
abstract: During somitogenesis, epithelial somites form from the pre-somitic mesoderm (PSM) in a periodic manner. This periodicity is regulated by a molecular oscillator, known as the 'segmentation clock', that is characterised by an oscillatory pattern of gene expression that sweeps the PSM in a caudal-rostral direction. Key components of the segmentation clock are intracellular components of the Notch, Wnt and FGF pathways, and it is widely accepted that intracellular negative-feedback loops regulate oscillatory gene expression. However, an open question in the field is how intracellular oscillations are coordinated, in the form of spatiotemporal waves of expression, across the PSM. In this study, we provide a potential mechanism for this process. We show at the mRNA level that the Notch1 receptor and Delta-like 1 (Dll1) ligand vary dynamically across the PSM of both chick and mouse. Remarkably, we also demonstrate similar dynamics at the protein level; hence, the pathway components that mediate intercellular coupling themselves exhibit oscillatory dynamics. Moreover, we quantify the dynamic expression patterns of Dll1 and Notch1, and show they are highly correlated with the expression patterns of two known clock components [Lfng mRNA and the activated form of the Notch receptor (cleaved Notch intracellular domain, NICD)]. Lastly, we show that Notch1 is a target of Notch signalling, whereas Dll1 is Wnt regulated. Regulation of Dll1 and Notch1 expression thus links the activity of Wnt and Notch, the two main signalling pathways driving the clock.
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bone
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Charlotte S L
authors.initials: CS
authors.lastname: Bailey
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Wiedermann
authors.affiliation: School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ferjentsik
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Appleton
authors.affiliation: Division of Mathematics, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Murray
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Miguel
authors.initials: M
authors.lastname: Maroto
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK j.k.dale@dundee.ac.uk.
authors.forename: J Kim
authors.initials: JK
authors.lastname: Dale
mesh_terms: D000465:Algorithms; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D016695:Glycosyltransferases / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019170:Somites / Q000196:embryology*
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D051880:Receptors, Notch; D016695:Glycosyltransferases; C498392:Lfng protein, mouse
keywords: Notch signalling; Oscillations; Somitogenesis