From local resynchronization to global pattern recovery in the zebrafish segmentation clock

Abstract

Integrity of rhythmic spatial gene expression patterns in the vertebrate segmentation clock requires local synchronization between neighboring cells by Delta-Notch signaling and its inhibition causes defective segment boundaries. Whether deformation of the oscillating tissue complements local synchronization during patterning and segment formation is not understood. We combine theory and experiment to investigate this question in the zebrafish segmentation clock. We remove a Notch inhibitor, allowing resynchronization, and analyze embryonic segment recovery. We observe unexpected intermingling of normal and defective segments, and capture this with a new model combining coupled oscillators and tissue mechanics. Intermingled segments are explained in the theory by advection of persistent phase vortices of oscillators. Experimentally observed changes in recovery patterns are predicted in the theory by temporal changes in tissue length and cell advection pattern. Thus, segmental pattern recovery occurs at two length and time scales: rapid local synchronization between neighboring cells, and the slower transport of the resulting patterns across the tissue through morphogenesis.

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

“…Intriguingly, similar rotating waves can be observed in explants obtained by mixing cells from different tails [18]. This behavior has also been observed in a recent model of Zebrafish somitogenesis starting from cells with randomized phases [51]. In these models the rotating waves become evident starting from more heterogeneous initial conditions.…”

Ripply suppresses Tbx6 to induce dynamic-to-static conversion in somite segmentation

“…Then, the number of cells in the domain is N = 41 for the wild type. To represent the posterior growth of embryos, we chose the reference at the tailbud [70][71][72] (Supplementary Fig. 11b).…”

Multistability and transitions between spatiotemporal patterns through versatile Notch-Hes signaling

“…The extensive multistability reported in the present study builds on several mechanisms and has some implications, notably for pattern selection in different contexts or between functional and spurious ones (Morelli et al, 2009;Palau-Ortin et al, 2015;Pfeuty and Kaneko, 2016;Uriu et al, 2021). Mulistationarity between spatial patterns typically arise from the combination of intrinsic bistability of cells and the intercellular positive feedback through Delta/Notch-mediated lateral inhibition (Collier et al, 1996;Wearing et al, 2000).…”

“…Notch-Hes pathway also contributes to cell-fate decision programs by antagonizing some fate-promoting factors and reciprocally (Roese-Koerner et al, 2016;Wahi et al, 2016;Sagner et al, 2018). This specific ability of Notch signaling pathway to elicit both oscillatory and switching activities is prone to give rise to diverse and complex spatiotemporal patterns of cell fates within tissues (Biga et al, 2021;Uriu et al, 2021), whose repertorie has yet to be fully explored and characterized.…”