Search

An important contribution of systems biology is the insight that biological systems depend on the function of molecular interactions and not just on individual molecules. System level mechanisms are particularly important in the development of animals and plants which depends not just on transcription factors and signaling molecules, but also on regulatory circuits and gene regulatory networks (GRNs). However, since GRNs consist of transcription factors, it can be challenging to assess the function of regulatory circuits independently of the function of regulatory factors. The comparison of different GRNs offers a way to do so and leads to several observations. First, similar regulatory circuits operate in various developmental contexts and in different species, and frequently, these circuits are associated with similar developmental functions. Second, given regulatory circuits are often used at particular positions within the GRN hierarchy. Third, in some GRNs, regulatory circuits are organized in a particular order in respect to each other. And fourth, the evolution of GRNs occurs not just by co-option of regulatory genes but also by rewiring of regulatory linkages between conserved regulatory genes, indicating that the organization of interactions is important. Thus, even though in most instances the function of regulatory circuits remains to be discovered, it becomes evident that the architecture and logic of GRNs are functionally important for the control of genome activity and for the specification of the body plan.

Gene regulatory networks (GRNs) offer an unprecedented view on the genomic control of developmental and evolutionary processes. By regulating gene expression, GRNs control the molecular changes in genome activity that drive development and enable evolution. A lot remains to be learned about how GRNs control developmental mechanisms, and this volume provides just a snapshot of a growing field. Many bits and pieces of regulatory circuits have been discovered, or are currently being investigated, in different animals and particularly also in plants. In many developmental contexts, functional analyses of GRNs are starting to illuminate the control systems that generate causality in the developmental process. This volume focuses in particular on developmental systems where decades of research have provided sufficient tools and insights to generate a causal understanding of the underlying GRNs and the evolution thereof. The articles in this collection discuss current insights into how GRNs operate in various contexts in development and evolution, and also address some of the challenges that lie ahead and that will be solved in coming years as research in this scientific area advances.

One of the signatures of evolutionarily related cell types is the expression of similar combinations of transcription factors in distantly related animals. Here we present evidence that sea urchin larvae possess bilateral clusters of ciliary photoreceptors that are positioned in the oral/anterior apical neurogenic domain and associated with pigment cells. The expression of synaptotagmin indicates that the photoreceptors are neurons. Immunostaining shows that the sea urchin photoreceptors express an RGR/GO-opsin, opsin3.2, which co-localizes with tubulin on immotile cilia on the cell surface. Furthermore, orthologs of several transcription factors expressed in vertebrate photoreceptors are expressed in sea urchin ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx, a transcription factor typically associated with ciliary photoreceptors. Analysis of gene expression during sea urchin development indicates that the photoreceptors derive from the anterior apical neurogenic domain. Thus, based on location, developmental origin, and transcription factor expression, sea urchin ciliary photoreceptors are likely homologous to vertebrate rods and cones. However, we found that genes typically involved in eye development in many animals, including pax6, six1/2, eya, and dac, are not expressed in sea urchin ciliary photoreceptors. Instead, all four genes are co-expressed in the hydropore canal, indicating that these genes operate as a module in an unrelated developmental context. Thus, based on current evidence, we conclude that at least within deuterostomes, ciliary photoreceptors share a common evolutionary origin and express a shared regulatory state that includes Rx, Otx, and Six3, but not transcription factors that are commonly associated with the retinal determination circuit.

The discovery of gene regulatory networks (GRNs) has opened a gate to access the genomic mechanisms controlling development. GRNs are systems of transcriptional regulatory circuits that control the differential specification of cell fates during development by regulating gene expression. The experimental analysis of GRNs involves a collection of methods, each revealing aspects of the overall control process. This review provides an overview of experimental and computational methods that have been successfully applied for solving developmental GRNs in the sea urchin embryo. The key in this approach is to obtain experimental evidence for functional interactions between transcription factors and regulatory DNA. In the second part of this review, a more generally applicable strategy is discussed that shows a path from experimental evidence to annotation of regulatory linkages to the generation of GRN models.

The insight that the genomic control of developmental process is encoded in the form of gene regulatory networks has profound impacts on many areas of modern bioscience. Most importantly, it affects developmental biology itself, as it means that a causal understanding of development requires knowledge of the architecture of regulatory network interactions. Furthermore, it follows that functional changes in developmental gene regulatory networks have to be considered as a primary mechanism for evolutionary process. We here discuss some of the recent advances in gene regulatory network biology and how they have affected our current understanding of development, evolution, and regulatory genomics.

“In times when we are flooded with information, in biology and elsewhere, it might be more important than ever to reflect upon the ways by which we acquire and organize information in order to expand current knowledge. Long decades of scientific research have produced so many thoughts and concepts and open questions, many of which can only now be adequately addressed, with the techniques to acquire large scale experimental data at many different levels of biological organization, from nucleic acid to morphology. How current insights can be used to generate a framework concept, and how such framework plus current technology can be used to access what is not yet known is not just of philosophical concern, but of crucial importance for the ability of systems biology approaches to contribute to the solution of some of the long-standing questions in biology, and to formulate new ideas and concepts.”

In our time, the sheer volume of published experimental measurements, their scope and technical sophistication, compounded with a proliferation of diverse approaches, objectives, and model systems, has made it particularly difficult to see the conceptual forest for the trees. Yet all of the elegant and sophisticated though disparate and unconnected data sets with which we are confronted represent biological output of the same fundamental operating principles. Each experimental system provides a different window which offers a pathway to these principles. In this book we provide a conceptual framework that we hope will make accessible the principles by which the genomic control system operates developmental and evolutionary process. This framework grows from the realization that the most fundamental causal principles in biology, which distinguish biology from all other sciences, emerge from the existence and function of genomic information. From the genomic sequence are to be recovered the determinants of body plan development in animals. Of course, the processes of biology are subject to the same laws of physics and chemistry as are those of the inanimate world, but it is the genome that mandates biological organization. This is not a metaphor, it is a description of mechanisms that we can now begin to perceive as an unbroken chain of causal connections, leading from the A’s, C’s, G’s and T’s of the genomic DNA to the developmental formulation of the elements of the organism. The new field that is coalescing around the concepts of genomic information processing partakes of principles and evidence from systems biology, developmental molecular biology, various aspects of body plan evolution and phylogenetics, as well as biological engineering and computational modeling. We found it useful to select and incorporate insights from all of these fields, where these illuminate the genomic control of development, without operating wholly within the paradigms of any one of th

Animals consist of body parts which are spatially discrete functional units. The spatial separation of these body parts and the diversification of their function and structure are developmentally controlled by gene regulatory networks. The transcription factors and signaling molecules which participate in the spatial organization of a developing organism are components of these networks. The causal linkages in the network consist of the regulatory interactions of each factor with its target genes. Interactions among different regulatory genes are responsible for forming specific spatial patterns of gene expression. The architecture of these regulatory interactions and how they instruct the formation of specific spatial domains is directly determined by the genomic sequence. In the sea urchin embryo, many such spatial domains are established early in development. A well-characterized gene regulatory network underlies the specification of endodermal and mesodermal regulatory domains in this embryo. We review multiple examples which reveal the causal logic underlying genomic control strategies for pattern formation during sea urchin embryogenesis.