Synchronised cycling gene oscillations in presomitic mesoderm cells require cell-cell contact

Abstract

Segmentation of the vertebrate body axis is initiated early in development with the sequential formation of somites. Somitogenesis is temporally regulated by a molecular oscillator, the segmentation clock, which acts within presomitic mesoderm (PSM) cells to drive periodic expression of the cyclic genes. We have investigated the kinetics of the progression of cycling gene expression along the PSM. Here we show that c-hairy1 and c-hairy2 mRNA expression traverses the PSM in an entirely progressive manner and that both these genes and c-Lfng maintain a similar anterior limit of expression during each cycle. However, some differences are seen regarding both the onset of a new oscillation of these genes and the duration of their expression in the caudal PSM. We also investigated whether oscillating cyclic gene expression in the PSM is entirely cell autonomous. We find that while small PSM explants are still able to maintain their oscillation schedule, once they are dissociated, PSM cells are no longer able to maintain synchronous oscillations. The results imply that cell communication or a community effect is essential for the normal pattern of cyclic gene expression in these cells.

Random cell movement promotes synchronization of the segmentation clock

“…Neighboring cells are in contact with each other (9,10). In the PSM, oscillatory expressions are synchronized among neighboring cells.…”

Coupling cellular oscillators: A mechanism that maintains synchrony against developmental noise in the segmentation clock

“…In contrast, the synchronized oscillation that is evident in the posterior PSM is the earliest and also the most common mode of oscillation in all of the vertebrate species examined so far (Bessho et al, 2003;Maroto et al, 2005), and thus should be the first target of clock oscillation studies.…”

“…At first glance, the segmentation clock appears to share similar features with the fireflies. Single PSM cells, when isolated and cultured, manage to keep cycling for a certain period of time, although their oscillation is unstable (Masamizu et al, 2006), and can communicate with signaling molecules in the PSM (Maroto et al, 2005). Furthermore, recent molecular and genetic analyses of both mutant mice and zebrafish have been used to propose a model that hairy-negative feedback lies at the core of the oscillator and also that Hairy-regulated (i.e., oscillator-linked) intercellular communication couples the individual oscillators (Fig.…”

Building the Spine: The Vertebrate Segmentation Clock

“…Mathematical modeling of the Notch extracellular loop connected to the fish Her1/Her7 oscillator further supports the proposed role of this pathway in coupling oscillations in nearby cells (Lewis 2003). Accordingly, dissociating the PSM cells-a procedure expected to impair Notch signaling, which requires cell-cell interactions-from chick embryos rapidly results in a loss of synchronized oscillations (Maroto et al 2005). Similarly, dissociation of mouse PSM cells and analysis of their oscillations using a real-time luciferase-based reporter fused to the Hes1 promoter show that dissociated cells exhibit very chaotic oscillatory patterns (Masamizu et al 2006).…”