RRC ID 58304
Author Yoshioka-Kobayashi K, Matsumiya M, Niino Y, Isomura A, Kori H, Miyawaki A, Kageyama R.
Title Coupling delay controls synchronized oscillation in the segmentation clock.
Journal Nature
Abstract Individual cellular activities fluctuate but are constantly coordinated at the population level via cell-cell coupling. A notable example is the somite segmentation clock, in which the expression of clock genes (such as Hes7) oscillates in synchrony between the cells that comprise the presomitic mesoderm (PSM)1,2. This synchronization depends on the Notch signalling pathway; inhibiting this pathway desynchronizes oscillations, leading to somite fusion3-7. However, how Notch signalling regulates the synchronicity of HES7 oscillations is unknown. Here we establish a live-imaging system using a new fluorescent reporter (Achilles), which we fuse with HES7 to monitor synchronous oscillations in HES7 expression in the mouse PSM at a single-cell resolution. Wild-type cells can rapidly correct for phase fluctuations in HES7 oscillations, whereas the absence of the Notch modulator gene lunatic fringe (Lfng) leads to a loss of synchrony between PSM cells. Furthermore, HES7 oscillations are severely dampened in individual cells of Lfng-null PSM. However, when Lfng-null PSM cells were completely dissociated, the amplitude and periodicity of HES7 oscillations were almost normal, which suggests that LFNG is involved mostly in cell-cell coupling. Mixed cultures of control and Lfng-null PSM cells, and an optogenetic Notch signalling reporter assay, revealed that LFNG delays the signal-sending process of intercellular Notch signalling transmission. These results-together with mathematical modelling-raised the possibility that Lfng-null PSM cells shorten the coupling delay, thereby approaching a condition known as the oscillation or amplitude death of coupled oscillators8. Indeed, a small compound that lengthens the coupling delay partially rescues the amplitude and synchrony of HES7 oscillations in Lfng-null PSM cells. Our study reveals a delay control mechanism of the oscillatory networks involved in somite segmentation, and indicates that intercellular coupling with the correct delay is essential for synchronized oscillation.
Volume 580(7801)
Pages 119-123
Published 2020-4-1
DOI 10.1038/s41586-019-1882-z
PII 10.1038/s41586-019-1882-z
PMID 31915376
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / analysis Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Biological Clocks / physiology* Calcium-Binding Proteins / metabolism Embryonic Development / physiology* Female Genes, Reporter / genetics Glycosyltransferases / deficiency Glycosyltransferases / genetics Male Mice Optogenetics Receptors, Notch / metabolism Signal Transduction Single-Cell Analysis Somites / cytology Somites / metabolism* Time Factors
IF 42.779
Times Cited 5
DNA material Achilles/pRSETB (RDB15982)