title: Oscillatory control of Delta-like1 in somitogenesis and neurogenesis: A unified model for different oscillatory dynamics.
abstract: During somite segmentation, mRNA expression of the mouse Notch ligand Delta-like1 (Dll1) oscillates synchronously in the presomitic mesoderm (PSM). However, the dynamics of Dll1 protein expression were rather controversial, and their functional significance was not known. Recent live-imaging analysis showed that Dll1 protein expression also oscillates synchronously in the PSM. Interestingly, accelerated or delayed Dll1 expression by shortening or elongating the Dll1 gene, respectively, dampens or quenches Dll1 oscillation at intermediate levels, a phenomenon known as "amplitude/oscillation death" of coupled oscillators in mathematical modeling. Under this condition, oscillation of the Notch effector Hes7 is also dampened, leading to severe fusion of somites and their derivatives, such as vertebrae and ribs. Thus, the appropriate timing of Dll1 expression is critical for its oscillatory expression, pointing to the functional significance of Dll1-mediated oscillatory cell-cell interactions in the segmentation clock. In neural stem cells, Dll1 expression is also oscillatory, but non-synchronous, and when Dll1 oscillation is dampened, oscillation of another Notch effector, Hes1, is also dampened, leading to defects of neural development. In this review, we discuss the underlying mechanism for the different oscillatory dynamics (synchronous versus non-synchronous) in the PSM and neural stem cells in a unified manner.
authors.affiliation: Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan; World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan. Electronic address: hshimojo@virus.kyoto-u.ac.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shimojo
authors.affiliation: Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan; World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan; Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Kyoto University Graduate School of Biostudies, Kyoto 606-8501, Japan. Electronic address: rkageyam@virus.kyoto-u.ac.jp.
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
mesh_terms: D000818:Animals; D019521:Body Patterning; D002135:Calcium-Binding Proteins; D047108:Embryonic Development; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch
keywords: Delta-like1; Neurogenesis; Oscillatory expression; Somitogenesis