Combinatorial regulatory states define cell fate diversity during embryogenesis.

Cell fate specification occurs along invariant species-specific trajectories that define the animal body plan. This process is controlled by gene regulatory networks that regulate the expression of the limited set of transcription factors encoded in animal genomes. Here we globally assess the spatial expression of ~90% of expressed transcription factors during sea urchin development from embryo to larva to determine the activity of gene regulatory networks and their regulatory states during cell fate specification.

Homologous gene regulatory networks control development of apical organs and brains in Bilateria.

Apical organs are relatively simple larval nervous systems. The extent to which apical organs are evolutionarily related to the more complex nervous systems of other animals remains unclear. To identify common developmental mechanisms, we analyzed the gene regulatory network (GRN) controlling the development of the apical organ in sea urchins.

Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation.

Background: The evolutionary history of cell types provides insights into how morphological and functional complexity arose during animal evolution. Photoreceptor cell types are particularly broadly distributed throughout Bilateria; however, their evolutionary relationship is so far unresolved. Previous studies indicate that ciliary photoreceptors are homologous at least within chordates, and here, we present evidence that a related form of this cell type is also present in echinoderm larvae.

The function of architecture and logic in developmental gene regulatory networks.

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.

Methods for the experimental and computational analysis of gene regulatory networks in sea urchins.

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.

Assessing regulatory information in developmental gene regulatory networks.

Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory information at different levels of network organization, from single node to subcircuit to large-scale GRNs and discuss how regulatory design features such as network architecture, hierarchical organization, and -regulatory logic contribute to the developmental function of network circuits.

Regulatory states in the developmental control of gene expression.

A growing body of evidence shows that gene expression in multicellular organisms is controlled by the combinatorial function of multiple transcription factors. This indicates that not the individual transcription factors or signaling molecules, but the combination of expressed regulatory molecules, the regulatory state, should be viewed as the functional unit in gene regulation. Here, I discuss the concept of the regulatory state and its proposed role in the genome-wide control of gene expression.

Sequential Response to Multiple Developmental Network Circuits Encoded in an Intronic cis-Regulatory Module of Sea Urchin hox11/13b.

Gene expression in different spatial domains is often controlled by separate cis-regulatory modules (CRMs), but regulatory states determining CRM activity are not only distinct in space, they also change continuously during developmental time. Here, we systematically analyzed the regulatory sequences controlling hox11/13b expression and identified a single CRM required throughout embryonic gut development. We show that within this CRM, distinct sets of binding sites recognizing Ets, Tcf, and homeodomain transcription factors control the dynamic spatial expression of hox11/13b in each developmental phase.

Implications of Developmental Gene Regulatory Networks Inside and Outside Developmental Biology.

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.

Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo.

Wnt signaling affects cell-fate specification processes throughout embryonic development. Here we take advantage of the well-studied gene regulatory networks (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene regulatory functions of the entire Wnt-signaling system. Five wnt genes, three frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf genes are expressed in dynamic spatial patterns in the pregastrular embryo of Strongylocentrotus purpuratus.

Encoding regulatory state boundaries in the pregastrular oral ectoderm of the sea urchin embryo.

By gastrulation the ectodermal territories of the sea urchin embryo have developed an unexpectedly complex spatial pattern of sharply bounded regulatory states, organized orthogonally with respect to the animal/vegetal and oral/aboral axes of the embryo. Although much is known of the gene regulatory network (GRN) linkages that generate these regulatory states, the principles by which the boundaries between them are positioned and maintained have remained undiscovered. Here we determine the encoded genomic logic responsible for the boundaries of the oral aspect of the embryo that separate endoderm from ectoderm and ectoderm from neurogenic apical plate and that delineate the several further subdivisions into which the oral ectoderm per se is partitioned.

A new software package for predictive gene regulatory network modeling and redesign.

The efficacy of a newly created software package for predictive modeling of developmental gene regulatory networks (GRNs) has recently been demonstrated (Peter et al., 2012 ). The program GeNeTool computes spatial gene expression patterns based on GRN interactions and thereby allows the direct comparison of predicted and observed spatial expression patterns.

Predictive computation of genomic logic processing functions in embryonic development.

Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model.

Transphyletic conservation of developmental regulatory state in animal evolution.

Specific regulatory states, i.e., sets of expressed transcription factors, define the gene expression capabilities of cells in animal development.

A gene regulatory network controlling the embryonic specification of endoderm.

Specification of endoderm is the prerequisite for gut formation in the embryogenesis of bilaterian organisms. Modern lineage labelling studies have shown that in the sea urchin embryo model system, descendants of the veg1 and veg2 cell lineages produce the endoderm, and that the veg2 lineage also gives rise to mesodermal cell types. It is known that Wnt/β-catenin signalling is required for endoderm specification and Delta/Notch signalling is required for mesoderm specification.

Evolution of gene regulatory networks controlling body plan development.

Evolutionary change in animal morphology results from alteration of the functional organization of the gene regulatory networks (GRNs) that control development of the body plan. A major mechanism of evolutionary change in GRN structure is alteration of cis-regulatory modules that determine regulatory gene expression. Here we consider the causes and consequences of GRN evolution.

Modularity and design principles in the sea urchin embryo gene regulatory network.

The gene regulatory network (GRN) established experimentally for the pre-gastrular sea urchin embryo provides causal explanations of the biological functions required for spatial specification of embryonic regulatory states. Here we focus on the structure of the GRN which controls the progressive increase in complexity of territorial regulatory states during embryogenesis; and on the types of modular subcircuits of which the GRN is composed. Each of these subcircuit topologies executes a particular operation of spatial information processing.

The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage.

As the result of early specification processes, sea urchin embryos eventually form various mesodermal cell lineages and a gut consisting of fore-, mid- and hindgut. The progression of specification as well as the overall spatial organization of the organism is encoded in its gene regulatory networks (GRNs). We have analyzed the GRN driving endoderm specification up to the onset of gastrulation and present in this paper the mechanisms which determine this process up to mid-blastula stage.

Genomic control of patterning.

The development of multicellular organisms involves the partitioning of the organism into territories of cells of specific structure and function. The information for spatial patterning processes is directly encoded in the genome. The genome determines its own usage depending on stage and position, by means of interactions that constitute gene regulatory networks (GRNs).