Different species develop at different rates. For example, equivalent developmental processes, often underpinned by the same genetic programmes, take longer in the human embryo than they do in the mouse. However, the basis of species-specific ‘tempo’ is challenging to elucidate, as many aspects of gene regulation might affect tempo. Examples are protein stability, post-translational modifications and mRNA splicing, which can also affect each other. Here, Charlotte Manser and Ruben Perez-Carrasco take a mathematical modelling approach to explore the basis of tempo. They consider the ‘orbits’ travelled by cells in the space of cell states. The exact temporal trajectories taken along each orbit may differ, but the orbit will conserve the relative sequence of events, preserving the function of the genetic program. This framework allows the authors to identify perturbations that change the tempo of a given developmental process but leave its sequence of events intact. Applying this model to neuronal precursor differentiation shows that rescaling the rates of both protein production and degradation can explain the different tempos of neural progenitor differentiation in mice and humans without changing the orbit of this conserved developmental process. Overall, this study provides a framework to identify the molecular mechanisms that underpin the timing of developmental processes.
