Oscillatory gene expression and somitogenesis

Abstract

A bilateral pair of somites forms periodically by segmentation of the anterior ends of the presomitic mesoderm (PSM). This periodic event is regulated by a biological clock called the segmentation clock, which involves cyclic gene expression. Expression of her1 and her7 in zebrafish and Hes7 in mice oscillates by negative feedback, and mathematical models have been used to generate and test hypotheses to aide elucidation of the role of negative feedback in regulating oscillatory expression. her/Hes genes induce oscillatory expression of the Notch ligand deltaC in zebrafish and the Notch modulator Lunatic fringe in mice, which lead to synchronization of oscillatory gene expression between neighboring PSM cells. In the mouse PSM, Hes7 induces coupled oscillations of Notch and Fgf signaling, while Notch and Fgf signaling cooperatively regulate Hes7 oscillation, indicating that Hes7 and Notch and Fgf signaling form the oscillator networks. Notch signaling activates, but Fgf signaling represses, expression of the master regulator for somitogenesis Mesp2, and coupled oscillations in Notch and Fgf signaling dissociate in the anterior PSM, which allows Notch signaling-induced synchronized cells to express Mesp2 after these cells are freed from Fgf signaling. These results together suggest that Notch signaling defines the prospective somite region, while Fgf signaling regulates the pace of segmentation. It is likely that these oscillator networks constitute the core of the segmentation clock, but it remains to be determined whether as yet unknown oscillators function behind the scenes.

Notch-mediated lateral inhibition regulates proneural wave propagation when combined with EGF-mediated reaction diffusion

“…Additionally, the combinatorial action of Notch and EGF signaling controls the maintenance of neural stem cells and neural progenitor cells (44). Similarly, vertebrate segmentation is controlled by the interplay between Notch and FGF (11). Notch signaling controls the synchronization between neighboring cells and positively regulates boundary formation by activating Mesp2.…”

“…For example, vertebrate segmentation is controlled by the interplay between Notch and FGF, including multiple negative feedbacks. Interdisciplinary approaches have revealed that oscillatory gene networks constitute the segmentation clock machinery (11,12).…”

Mobility-induced persistent chimera states

“…A biological system where our results could be relevant is the vertebrate segmentation clock. The segmentation clock is a tissue generating dynamic patterns that acts during embryonic development and is responsible for the segmented repetitive structure of the vertebrate body axis [8,[68][69][70]. It consists of a population of genetic oscillators at the cellular level [71] which are coupled through a local communication mechanism [72][73][74].…”

A novel targeted Lunatic fringe allele predicted to reduce protein secretion is dominant and disrupts somitogenesis

“…In the PSM, several genes exhibit oscillatory expression, with a cyclic period that matches the rate of somite formation, linking them to the segmentation clock. Many of these genes are members of the Notch pathway, although genes in the FGF and WNT pathways also exhibit cyclic expression (reviewed by Kageyama et al, 2012). Notch activity levels in the PSM also oscillate (Morimoto et al, 2005;, and in mouse and chicken this requires periodic repression of Notch signaling by lunatic fringe (Lfng), which functions in a delayed negative-feedback loop with the transcriptional repressor Hes7 to regulate cyclic Notch activation in the clock (Bessho et al, 2003;Kageyama et al, 2012).…”