Species-specific segmentation clock periods are due to differential biochemical reaction speeds

Abstract

Although mechanisms of embryonic development are similar between mice and humans, the time scale is generally slower in humans. To investigate these interspecies differences in development, we recapitulate murine and human segmentation clocks that display 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Our interspecies genome-swapping analyses indicate that the period difference is not due to sequence differences in the HES7 locus, the core gene of the segmentation clock. Instead, we demonstrate that multiple biochemical reactions of HES7, including the degradation and expression delays, are slower in human cells than they are in mouse cells. With the measured biochemical parameters, our mathematical model accounts for the two- to threefold period difference between the species. We propose that cell-autonomous differences in biochemical reaction speeds underlie temporal differences in development between species.

Mapping Transcriptomic Vector Fields of Single Cells

“…SI 2B right ). This result complements the conclusion of (Matsuda et al 2020; Rayon et al 2020), which was based on a small set of human proteins (Battich et al 2020) that have half-lives roughly twice as long as their mouse counterparts. Log-likelihood and R-square values (see MATERIAL AND METHODS ) calculated based on observed data and estimated values from the curve-fitting and linear regression, respectively, confirm that parameter estimations confidently fit the data for the degradation and kinetics experiments ( Fig.…”

“…Our estimated kinetic rate constants, which are more accurate than those obtained using the original RNA velocity method, provided multiple functional insights, including the high synthesis rates of mitochondrial genes and the global and proportional increase in RNA stability of human genes relative to their mouse orthologs. The latter observation expands on recent findings that biochemical reactions, especially protein degradation, are consistently slower in human cells than in their mouse counterparts during both embryonic segmentation (Matsuda et al 2020) and motor neuron differentiation (Rayon et al 2020). By jointly analyzing intron/exon and labeling information from tscRNA-seq experiments, we reconcile the kinetics obtained by metabolic labeling with those obtained with RNA splicing, unexpectedly revealing a subset of RNAs with slower splicing than degradation.…”

An Evolutionary Perspective of Dyslexia, Stress, and Brain Network Homeostasis

“…Of fundamental importance to understanding the merits of an adversity/plasticity/attention networks and reading connection, the human brain is highly neotenous (Somel et al, 2009;Bufill et al, 2011;Petanjek et al, 2011;Somel et al, 2011;Liu et al, 2012;Miller et al, 2012;Somel et al, 2014;Matsuda et al, 2020). Neoteny, or developmental allochrony, refers to the prolongation of high cortical metabolism and synaptic plasticity in regional neocortical areas in humans compared to other primates.…”

A Picture Worth a Thousand Molecules—Integrative Technologies for Mapping Subcellular Molecular Organization and Plasticity in Developing Circuits

“…Because protein turnover helps set the tempo for embryonic development, changes in turnover rate may have important impacts on synaptogenesis and plasticity (Alvarez-Castelao and Schuman, 2015; Matsuda et al, 2020;Rayon et al, 2020). To investigate the nascent synaptic proteome and protein metabolic turnover, newly synthesized proteins can be selectively tagged during the translation process (Cohen and Ziv, 2019).…”