How enhancers regulate wavelike gene expression patterns.

A key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called 'enhancers.' Much of our models of how enhancers work rely on the assumption that genes are activated de novo as stable domains across embryonic tissues.

Patterning with clocks and genetic cascades: Segmentation and regionalization of vertebrate versus insect body plans.

Oscillatory and sequential processes have been implicated in the spatial patterning of many embryonic tissues. For example, molecular clocks delimit segmental boundaries in vertebrates and insects and mediate lateral root formation in plants, whereas sequential gene activities are involved in the specification of regional identities of insect neuroblasts, vertebrate neural tube, vertebrate limb, and insect and vertebrate body axes. These processes take place in various tissues and organisms, and, hence, raise the question of what common themes and strategies they share.

Geometric models for robust encoding of dynamical information into embryonic patterns.

During development, cells gradually assume specialized fates via changes of transcriptional dynamics, sometimes even within the same developmental stage. For anterior-posterior (AP) patterning in metazoans, it has been suggested that the gradual transition from a dynamic genetic regime to a static one is encoded by different transcriptional modules. In that case, the static regime has an essential role in pattern formation in addition to its maintenance function.

Speeding up anterior-posterior patterning of insects by differential initialization of the gap gene cascade.

Recently, it was shown that anterior-posterior patterning genes in the red flour beetle Tribolium castaneum are expressed sequentially in waves. However, in the fruit fly Drosophila melanogaster, an insect with a derived mode of embryogenesis compared to Tribolium, anterior-posterior patterning genes quickly and simultaneously arise as mature gene expression domains that, afterwards, undergo slight posterior-to-anterior shifts. This raises the question of how a fast and simultaneous mode of patterning, like that of Drosophila, could have evolved from a rather slow sequential mode of patterning, like that of Tribolium.

A re-inducible gap gene cascade patterns the anterior-posterior axis of insects in a threshold-free fashion.

Gap genes mediate the division of the anterior-posterior axis of insects into different fates through regulating downstream hox genes. Decades of tinkering the segmentation gene network of led to the conclusion that gap genes are regulated (at least initially) through a threshold-based mechanism, guided by both anteriorly- and posteriorly-localized morphogen gradients. In this paper, we show that the response of the gap gene network in the beetle upon perturbation is consistent with a threshold-free 'Speed Regulation' mechanism, in which the speed of a genetic cascade of gap genes is regulated by a posterior morphogen gradient.

Enhancer identification and activity evaluation in the red flour beetle, .

Evolution of -regulatory elements (such as enhancers) plays an important role in the production of diverse morphology. However, a mechanistic understanding is often limited by the absence of methods for studying enhancers in species other than established model systems. Here, we sought to establish methods to identify and test enhancer activity in the red flour beetle, To identify possible enhancer regions, we first obtained genome-wide chromatin profiles from various tissues and stages of using FAIRE (formaldehyde-assisted isolation of regulatory elements)-sequencing.

Speed regulation of genetic cascades allows for evolvability in the body plan specification of insects.

During the anterior-posterior fate specification of insects, anterior fates arise in a nonelongating tissue (called the "blastoderm"), and posterior fates arise in an elongating tissue (called the "germband"). However, insects differ widely in the extent to which anterior-posterior fates are specified in the blastoderm versus the germband. Here we present a model in which patterning in both the blastoderm and germband of the beetle is based on the same flexible mechanism: a gradient that modulates the speed of a genetic cascade of gap genes, resulting in the induction of sequential kinematic waves of gap gene expression.

Shadow Enhancers Mediate Dynamic Shifts of Gap Gene Expression in the Drosophila Embryo.

Drosophila patterning genes often contain pairs of primary and shadow enhancers that possess overlapping activities [1-5]. It has been suggested that this regulatory "redundancy" helps ensure reliable activation of gene expression under stressful conditions such as increases in temperature [4, 5]. There is also evidence that shadow enhancers help produce sharp on/off boundaries of gene expression in response to small changes in the levels of regulatory factors, such as the maternal Bicoid gradient [6, 7].

Caudal regulates the spatiotemporal dynamics of pair-rule waves in Tribolium.

In the short-germ beetle Tribolium castaneum, waves of pair-rule gene expression propagate from the posterior end of the embryo towards the anterior and eventually freeze into stable stripes, partitioning the anterior-posterior axis into segments. Similar waves in vertebrates are assumed to arise due to the modulation of a molecular clock by a posterior-to-anterior frequency gradient. However, neither a molecular candidate nor a functional role has been identified to date for such a frequency gradient, either in vertebrates or elsewhere.

A segmentation clock operating in blastoderm and germband stages of Tribolium development.

In Drosophila, all segments form in the blastoderm where morphogen gradients spanning the entire anterior-posterior axis of the embryo provide positional information. However, in the beetle Tribolium castaneum and most other arthropods, a number of anterior segments form in the blastoderm, and the remaining segments form sequentially from a posterior growth zone during germband elongation. Recently, the cyclic nature of the pair-rule gene Tc-odd-skipped was demonstrated in the growth zone of Tribolium, indicating that a vertebrate-like segmentation clock is employed in the germband stage of its development.

Comparisons of the embryonic development of Drosophila, Nasonia, and Tribolium.

Studying the embryogenesis of diverse insect species is crucial to understanding insect evolution. Here, we review current advances in understanding the development of two emerging model organisms: the wasp Nasonia vitripennis and the beetle Tribolium castaneum in comparison with the well-studied fruit fly Drosophila melanogaster. Although Nasonia represents the most basally branching order of holometabolous insects, it employs a derived long germband mode of embryogenesis, more like that of Drosophila, whereas Tribolium undergoes an intermediate germband mode of embryogenesis, which is more similar to the ancestral mechanism.