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Abstract Numerous cellular and molecular processes during embryonic development prompt the fundamental question of how their tempos are coordinated and whether a common global modulator exists. While the segmentation clock tempo scales with the kinetics of gene expression and degradation processes of the core clock gene Hes7 across mammals, the coordination of these processes remains unclear. This study examines whether metabolic activities serve as a global modulator for the segmentation clock, finding them to be selective instead. Several metabolic inhibitions extend the clock period but affect key processes differently: glycolysis inhibition slows Hes7 protein degradation and production delay without altering intron delay, while electron transport chain inhibition extends intron delay without influencing the other processes. Combinations of distinct metabolic inhibitions exhibit synergistic effects. We propose that the scaled kinetics of segmentation clock processes across species may result from combined selective modulators shaped by evolutionary constraints, rather than a single global modulator.

Numerous cellular and molecular processes during embryonic development prompt the fundamental question of how their tempos are coordinated and whether a common global modulator exists. While the segmentation clock tempo scales with the kinetics of gene expression and degradation processes of the core clock gene Hes7 across mammals, the coordination of these processes remains unclear. This study examines whether metabolic activities serve as a global modulator for the segmentation clock, finding them to be selective instead. Several metabolic inhibitions extend the clock period but affect key processes differently: glycolysis inhibition slows Hes7 protein degradation and production delay without altering intron delay, while electron transport chain inhibition extends intron delay without influencing the other processes. Combinations of distinct metabolic inhibitions exhibit synergistic effects. We propose that the scaled kinetics of segmentation clock processes across species may result from combined selective modulators shaped by evolutionary constraints, rather than a single global modulator. Metabolism has been considered an attractive candidate as a global modulator of the tempo of multiple developmental processes, including somite segmentation timing. Here they demonstrate that metabolic activities instead selectively modulate individual segmentation clock processes. [ABSTRACT FROM AUTHOR]

The formation of the vertebrate body involves the coordinated production of trunk tissues from progenitors located in the posterior of the embryo. Although in vitro models using pluripotent stem cells replicate aspects of this process 1-10 , they lack crucial components, most notably the notochord-a defining feature of chordates that patterns surrounding tissues 11 . Consequently, cell types dependent on notochord signals are absent from current models of human trunk formation. Here we performed single-cell transcriptomic analysis of chick embryos to map molecularly distinct progenitor populations and their spatial organization. Guided by this map, we investigated how differentiating human pluripotent stem cells develop a stereotypical spatial organization of trunk cell types. We found that YAP inactivation in conjunction with FGF-mediated MAPK signalling facilitated WNT pathway activation and induced expression of TBXT (also known as BRA). In addition, timely inhibition of WNT-induced NODAL and BMP signalling regulated the proportions of different tissue types, including notochordal cells. This enabled us to create a three-dimensional model of human trunk development that undergoes morphogenetic movements, producing elongated structures with a notochord and ventral neural and mesodermal tissues. Our findings provide insights into the mechanisms underlying vertebrate notochord formation and establish a more comprehensive in vitro model of human trunk development. This paves the way for future studies of tissue patterning in a physiologically relevant environment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Regeneration is the replacement of lost or damaged tissue with a functional copy. In axolotls and zebrafish, regeneration involves stem cells produced by de-differentiation. These cells form a growth zone which expresses developmental patterning genes at its apex. This system resembles an embryonic developmental field where cells undergo pattern formation. Some lizards, including geckos, can regenerate their tails, but it is unclear whether they show a "development-like" regeneration pathway. Results: Using the tokay gecko (Gekko gecko) model species, we examined seven stages of tail regeneration, and three stages of embryonic tail bud development, using transcriptomics, single-cell sequencing, and in situ hybridization. We find no apical growth zone in the regenerating tail. The transcriptomes of the regenerating vs. embryonic tails are quite different with respect to developmental patterning genes. Posterior HOXC genes were activated in a temporally collinear sequence in the regenerating tail. The major precursor populations were stromal cells (regenerating tail) vs. pluripotent stem cells (embryonic tail). Segmented skeletal muscles were regenerated with no expression of classical segmentation genes, but with the early activation of satellite cell markers. Conclusions: Our study suggests that tail regeneration in the tokay gecko—unlike tail development—might rely on the activation of resident stem cells, guided by pre-existing positional information. [ABSTRACT FROM AUTHOR]