What sets the species-specific period of the segmentation clock? · revision history

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Title

What sets the species-specific period of the segmentation clock

Plain

The genetic oscillator that times backbone segments has a period of roughly 2 to 3 hours in mouse and about 5 hours in human cells grown in a dish. Which single cellular property slows every step of the clock by the same factor is not established.

Precise

For the Hes7 oscillator in presomitic mesoderm (period approximately $2.5\,\mathrm{h}$ in mouse and $5\,\mathrm{h}$ in human stem-cell-derived tissue), Matsuda and co-workers (2020) showed that protein degradation rates and expression delays scale together with the period, and Diaz-Cuadros and co-workers (2023) linked the period to mass-specific metabolic rate and the NAD+/NADH ratio. Identify the global variable that sets all these rates proportionally and give a model that predicts the clock period of at least four species from independent measurements of that variable.

Settled by

Measurements of the candidate global variable and of the clock period in stem-cell-derived presomitic mesoderm from several species, plus perturbations of that variable that shift the period by the predicted amount.

Kind

phenomenon

Answer type

mechanism

References

(empty)

Literature status

partially-resolved

Status note

Matsuda and co-workers (Science 2020, doi 10.1126/science.aba7668) and Diaz-Cuadros and co-workers (Nature 2023, doi 10.1038/s41586-022-05574-4) tied the period to reaction speeds and metabolism; what controls the global rate remains open.

Posed since

2020