Pulses of Notch activation synchronise oscillating somite cells and entrain the zebrafish segmentation clock

Soza‐Ried, Cristian; Öztürk, Emre; Ish‐Horowicz, David; Lewis, Julian

doi:10.1242/dev.102111

Cited by 55 publications

(53 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experimental and modeling data have demonstrated that the sweeping wave of segmentation clock oscillations may not even be necessary for proper somite formation (Hester et al, 2010;Soza-Ried et al, 2014). Although initiation of somite patterning may occur in the posterior PSM, additional patterning mechanisms also operate later.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of the slowing segmentation clock reveal alternating two-segment periodicity

et al. 2015

View full text Add to dashboard Cite

The formation of reiterated somites along the vertebrate body axis is controlled by the segmentation clock, a molecular oscillator expressed within presomitic mesoderm (PSM) cells. Although PSM cells oscillate autonomously, they coordinate with neighboring cells to generate a sweeping wave of cyclic gene expression through the PSM that has a periodicity equal to that of somite formation. The velocity of each wave slows as it moves anteriorly through the PSM, although the dynamics of clock slowing have not been well characterized. Here, we investigate segmentation clock dynamics in the anterior PSM in developing zebrafish embryos using an in vivo clock reporter, her1:her1-venus. The her1:her1-venus reporter has single-cell resolution, allowing us to follow segmentation clock oscillations in individual cells in real-time. By retrospectively tracking oscillations of future somite boundary cells, we find that clock reporter signal increases in anterior PSM cells and that the periodicity of reporter oscillations slows to about ∼1.5 times the periodicity in posterior PSM cells. This gradual slowing of the clock in the anterior PSM creates peaks of clock expression that are separated at a two-segment periodicity both spatially and temporally, a phenomenon we observe in single cells and in tissue-wide analyses. These results differ from previous predictions that clock oscillations stop or are stabilized in the anterior PSM. Instead, PSM cells oscillate until they incorporate into somites. Our findings suggest that the segmentation clock may signal somite formation using a phase gradient with a two-somite periodicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamics of the slowing segmentation clock reveal alternating two-segment periodicity

et al. 2015

View full text Add to dashboard Cite

show abstract

“…S12). In zebrafish, the Dll1 homolog DeltaC is expressed in an oscillatory manner and regulates their segmentation clock (Mara et al 2007;Soza-Ried et al 2014). Thus, the functional significance of the oscillatory expression of Notch ligands seems to be evolutionarily conserved among vertebrates such as mammals and zebrafish.…”

Section: Dynamic Control Of Dll1 In Cell-cell Interactionsmentioning

confidence: 99%

Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis

et al. 2016

View full text Add to dashboard Cite

Notch signaling regulates tissue morphogenesis through cell-cell interactions. The Notch effectors Hes1 and Hes7 are expressed in an oscillatory manner and regulate developmental processes such as neurogenesis and somitogenesis, respectively. Expression of the mRNA for the mouse Notch ligand Delta-like1 (Dll1) is also oscillatory. However, the dynamics of Dll1 protein expression are controversial, and their functional significance is unknown. Here, we developed a live-imaging system and found that Dll1 protein expression oscillated in neural progenitors and presomitic mesoderm cells. Notably, when Dll1 expression was accelerated or delayed by shortening or elongating the Dll1 gene, Dll1 oscillations became severely dampened or quenched at intermediate levels, as modeled mathematically. Under this condition, Hes1 and Hes7 oscillations were also dampened. In the presomitic mesoderm, steady Dll1 expression led to severe fusion of somites and their derivatives, such as vertebrae and ribs. In the developing brain, steady Dll1 expression inhibited proliferation of neural progenitors and accelerated neurogenesis, whereas optogenetic induction of Dll1 oscillation efficiently maintained neural progenitors. These results indicate that the appropriate timing of Dll1 expression is critical for the oscillatory networks and suggest the functional significance of oscillatory cell-cell interactions in tissue morphogenesis.

show abstract

“…Because oscillations of Hes1 and its related genes drive the oscillatory expression of the Notch ligand Dll1, the Delta-Notch pathway has been functionally implicated in cell-cell transfer of the oscillatory information (Jiang et al 2000;Okubo et al 2012;Bone et al 2014;Soza-Ried et al 2014;Shimojo et al 2016). However, there is no experimental evidence for the functional capabilities of Notch signaling molecules to transmit oscillatory information to adjacent cells.…”

Section: Entrainment Of the Endogenous Hes1 Oscillation By Dll1 Inputsmentioning

confidence: 99%

Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information

et al. 2017

View full text Add to dashboard Cite

Cells communicate with each other to coordinate their gene activities at the population level through signaling pathways. It has been shown that many gene activities are oscillatory and that the frequency and phase of oscillatory gene expression encode various types of information. However, whether or how such oscillatory information is transmitted from cell to cell remains unknown. Here, we developed an integrated approach that combines optogenetic perturbations and single-cell bioluminescence imaging to visualize and reconstitute synchronized oscillatory gene expression in signal-sending and signal-receiving processes. We found that intracellular and intercellular periodic inputs of Notch signaling entrain intrinsic oscillations by frequency tuning and phase shifting at the singlecell level. In this way, the oscillation dynamics are transmitted through Notch signaling, thereby synchronizing the population of oscillators. Thus, this approach enabled us to control and monitor dynamic cell-to-cell transfer of oscillatory information to coordinate gene expression patterns at the population level.

show abstract

Pulses of Notch activation synchronise oscillating somite cells and entrain the zebrafish segmentation clock

Cited by 55 publications

References 57 publications

Dynamics of the slowing segmentation clock reveal alternating two-segment periodicity

Dynamics of the slowing segmentation clock reveal alternating two-segment periodicity

Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis

Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information

Contact Info

Product

Resources

About