Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock

Abstract

The segmentation clock is an oscillating genetic network thought to govern the rhythmic and sequential subdivision of the elongating body axis of the vertebrate embryo into somites: the precursors of the segmented vertebral column. Understanding how the rhythmic signal arises, how it achieves precision and how it patterns the embryo remain challenging issues. Recent work has provided evidence of how the period of the segmentation clock is regulated and how this affects the anatomy of the embryo. The ongoing development of realtime clock reporters and mathematical models promise novel insight into the dynamic behavior of the clock.Key words: Gradient, Modeling, Negative feedback, Oscillator, Signaling, Somitogenesis IntroductionThe segmented anatomy of the vertebrate embryo is evident in the two bilaterally symmetrical rows of somites that flank the notochord along the body axis. These blocks of mesodermal cells give rise primarily to bone, muscle and skin of the adult body, which is correspondingly segmented. Somitogenesis is a rhythmic and sequential process in which each successive bilateral somite pair segregates at a regular time interval from the anterior end of the pre-somitic mesoderm (PSM, see Glossary, Box 1) as the body axis elongates (Fig. 1A,B). Somitogenesis has long been of interest to developmental biologists because it involves the coordination of patterning and growth of a tissue by a regularly repeated morphogenetic process. The topic of this review is the molecular segmentation clock that underlies this periodicity. The segmentation clock has attracted the attention of those interested in biological clocks and the molecular mechanisms of developmental timing, as well as those studying the function and stability of rapidly acting genetic circuits, and the interplay between the properties of single cells and their collective behavior at the tissue level. Finally, the rhythmic nature of the process is the seed for a theoretical interest in somitogenesis that is decades old and now promises a powerful synthesis of experiment and theory that is emblematic of modern embryology.This review first provides an overview of somitogenesis, then describes the prevailing dynamic model for somitogenesis, the Clock and Wavefront mechanism, its molecular phenomenology Development 139, 625-639 (2012) REVIEW Box 1. GlossaryBiological oscillator. A system that generates a periodic variation in the state of a cell, tissue or organism. The vibrating stereocillia bundles of inner ear hair cells, the contraction cycle of cardiac muscle cells, circadian clocks and rhythmic neuronal circuits are all biological oscillators. Coupling. Communication between neighboring oscillators that leads to mutual adjustment of their frequencies. For example, activation of Notch receptors in a presomitic mesoderm cell by Delta from neighboring cells can affect the dynamics of Notch pathway components in the target cell. Frequency profile. Dependence of the frequency of the oscillators in an array on their position. In the segmentat...

Systems biology and the integration of mechanistic explanation and mathematical explanation

“…Many molecular aspects underlying somite formation have been elucidated, e.g., by the analysis of mutants with defective segment formation, with zebrafish being the best explored model organism (Dequéant & Pourquié, 2008;Oates et al, 2012). The basic mechanism consists in the interaction of two processes: the segmentation clock consisting in synchronized cellular oscillations in the tissues where somites form, and a wavefront of a molecular substance moving with constant speed from the embryo's head to tail (where additional somites yet have to form).…”

Changing cell behaviours during beetle embryogenesis correlates with slowing of segmentation

“…Although segment formation was once assumed to be distinct between major taxa, some aspects now appear similar. Sequential segmentation has been studied most extensively in vertebrates, where it relies on regulatory interactions between a segmentation clock that oscillates in the posterior growth zone and a posteriorly moving wavefront that stabilizes the readout of the clock to produce segments [1][2][3] . The spatial periodic pattern of segmentation is derived from the temporal periodic pattern of oscillating gene expression (the 'segmentation clock') in the growth zone 4 .…”

Control of synthetic gene networks and its applications

“…Organization of individual cells into population wide patterns is a common behavior found throughout nature [28,97] and biomedical applications [29,98].…”