Modular control of time and space during vertebrate axis segmentation

Abstract

How temporal and spatial control of developmental processes are linked remains a fundamental question. Do underlying mechanisms form a single functional unit or are these dissociable modules? We address this question by studying the periodic process of embryonic axis segmentation, using genetic crosses of inbred medaka fish strains representing two species, Oryzias sakaizumii and latipes. Our analysis revealed correlated interspecies differences with regard to the timing of segmentation, the size of segments and of the presomitic mesoderm (PSM), from which segments are periodically formed. We then did interspecies crosses and real-time imaging quantifications, which revealed extensive phenotypic variation in ~600 F2 embryos. Importantly, while the F2 analysis showed correlated changes of PSM and segment size, these spatial measures were not correlated to the timing of segmentation. This shows that the control of time and space of axis segmentation can, in principle, be decoupled. In line with this finding, we identified, using developmental quantitative trait loci (devQTL) mapping, distinct chromosomal regions linked to either the control of segmentation timing or PSM size. We were able to validate the devQTL findings using a CRISPR/Cas9 loss-of-function approach on several candidate genes in vivo. Combined, this study reveals that a developmental constraint mechanism underlies spatial scaling of axis segmentation, while its spatial and temporal control are dissociable modules. Our findings emphasise the need to reveal the selective constraints linking these modules in the natural environment.

The stem cell zoo for comparative studies of developmental tempo

“…However, while PSC-derived models can recapitulate cell-intrinsic behaviors, they lack the ability to reproduce the complex environment and morphogenesis of the embryo. Xenotransplantation, species hybridization, or interspecies chimerism are useful approaches to address the importance of extrinsic factors in the establishment of species-specific behaviors in vivo 26 , 67 , 68 . The combination of the stem cell zoo with embryological data is essential to avoid in vitro artifacts and have a comprehensive understanding of how developmental tempo emerges across species.…”

Species-specific roles of the Notch ligands, receptors, and targets orchestrating the signaling landscape of the segmentation clock

“…Another advantage that Medaka has for decoding the genetics underlying species-specific clock times is that different inbred Medaka sub-species show different her7 clock periods ( Seleit et al, 2023 ). They also have variable PSM and somite lengths, which positively correlate with clock periodicity.…”

“…Crossbreeding species with different periods provides a useful approach to understand the genetic basis of clock periodicity. Accordingly, intercrossing these different Medaka species results in a wide range of meiotic recombination across the genome, yielding F2 progeny showing a wide range of clock periods ( Seleit et al, 2023 ). The authors further show that while clock period scales with PSM size in parental fishes, these two parameters do not correlate in F2 progeny.…”