A Clock and Wavefront Self-Organizing Model Recreates the Dynamics of Mouse Somitogenesis in-vivo and in-vitro

Abstract

During mouse development, presomitic mesoderm cells synchronize oscillations of Wnt and Notch signaling forming sequential waves that pattern somites. Tail explants have shown that these waves can be formed in the absence of global embryonic signals in vitro but the self-organizing mechanism that underlies this process remains unknown. Here, we present a model called Sevilletor that synchronizes two oscillatory reactants via local cell communication to generate a variety of self-organizing patterns. This model provides a unifying minimal framework to study somitogenesis showing that classical models cannot recapitulate the waves formed in explants. Nevertheless, we show that explant patterning can be recapitulated by an extended Clock and Wavefront model where Fgf and Retinoic acid signals modulate a self-organizing oscillator implemented by Wnt and Notch. This model captures the change in relative phase of Wnt and Notch observed in mouse and explains how cells can be excited to oscillate by local cell communication.

The first embryo, the origin of cancer and animal phylogeny. IV. The neoplastic basis for the formation of the innate immune system

“…Scientists have avoided discussing biological (molecular/genetic) clocks as mechanical (Hubaud et al, 2017). But segmentation of somites, classically a biological clock (Dubrulle and Pourquie, 2002;Pourquie, 2003;Andrade et al, 2007;Klepstad and Marcon, 2023), is evidently subjected to tensile forces of elongation and folding (Mongera et al, 2019;Anand et al, 2023;Yaman and Ramanathan, 2023). Thus, in the context of this hypothesis, mechanical memory (like a clock) will explain how germ cells manage to rebuild all structural coherence in the next generation; these topics are discussed in a separate article (Cofre, 2022).…”

Amphibian segmentation clock models suggest mechanisms of slowed development across increasing genome size and nuclear volume

“…Somitogenesis is typically described as operating through a clock and wavefront mechanism in which cell-autonomous oscillations of a somitogenesis gene (i.e. the "segmentation clock") interact with Notch, Wnt, FGF, and retinoic acid pathways across the PSM tissue to coordinate proper timing of segmentation of groups of neighboring cells into bilateral pairs of somites (Aulehla and Pourquié 2010, Cooke and Zeeman 1976, Gibb et al 2010, Klepstad and Marcon 2023. The segmentation clock operates via oscillatory gene expression at the single-cell level, while the wavefront takes place at the intercellular level across the PSM.…”