ScienceWeek

DEVELOPMENTAL BIOLOGY: MODELS OF BIOLOGICAL OSCILLATORS

The following points are made by O. Pourquié and A. Goldbeter (Current Biology 2003 13:R632):

1) The study of biological oscillators has for long been a major focus of interest for theoretical biologists. Complex models of the cell cycle or circadian clocks have been elaborated in the past few years. In developmental biology, few examples of oscillators have been identified. The best characterized example so far is the segmentation clock, a transcriptional oscillator involved in the control of the segmentation of the body axis. While a wealth of data has accumulated on this oscillator over the past few years, no modelling attempts based on these data have been reported until recently.

2) The body of a vertebrate animal is formed by a series of repeated blocks called segments, which include structures such as vertebrae, muscles and peripheral nerves. This segmental pattern of the body axis is established early in embryogenesis through the rhythmic production of the somites, paired blocks of paraxial mesoderm which bud off sequentially from the anterior extremity of the presomitic mesoderm. The segmentation clock drives the periodic transcription in the presomitic mesoderm of so-called "cyclic genes", most of which are related to the Notch signalling pathway.

3) Lewis (2003) proposes a theoretical model which integrates the different components of the zebra fish oscillator. The proposed model is based on a negative feedback loop with a transcriptional delay. It accounts for the transcriptional oscillations produced by the segmentation clock. This study is complemented by a report by Monk (2003), which extends this modelling approach to other oscillations based on transcriptional loops recently uncovered. The reports by Lewis and Monk illustrate the usefulness of theoretical models for comprehending the dynamics of regulated cellular processes. Both studies show that mathematical models provide an important tool for analyzing dynamic phenomena that cannot be predicted on the basis of sheer intuition.

Current Biology http://www.current-biology.com

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COMPUTER MODELS OF INVERTEBRATE SEGMENTATION

The following points are made by Eors Szathmary (Nature 2001 411:143):

1) It has long been known that the beginning and the end of embryological development are variable traits in evolution. Diversity at an early developmental stage (in the mechanism of gastrulation, for example) can be attributed to evolutionary adaptations to the ecological setting in which the embryo begins to unfold. The later phases must also differ, otherwise species would all look the same. For example, development in parasitic wasps has diverged widely. Early cell divisions of the fertilized egg, establishment of head-to-tail polarity, and the genetic circuit for body segmentation have all been modified, apparently as adaptations to the parasitic life-style.

2) But developmental malleability can go beyond this. Although the external appearance of an organism may be fixed, the genetic network, in which genes switch one another on and off so that programmed development runs successfully, seems to be changeable. This is analogous to rewiring a computer without changing the housing.

3) Segmentation, including stripes on animal coats, fascinated the mathematician Alan Turing (1912-1954), who in 1952 proposed a mechanism for pattern formation. Turing demonstrated that in a chemical system that begins as spatially homogeneous, a diffusing activator and an inhibitor could give rise to stationary wave-like concentration profiles of chemicals.

4) Similar reaction-diffusion mechanisms may be at work in some biological systems, but other systems, previously thought to be Turing systems, such as stripe formation in the fruit fly Drosophila, apparently use a mechanism in which stripe identity is determined by differing combinations of regulatory elements, following an initial spatial heterogeneity, with the underlying genetic circuit having a hierarchical structure.

Nature http://www.nature.com/nature

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