The network of interacting regulatory signals within a cell comprises one of the most complex and powerful computational systems in biology. Gene regulatory networks play a key role in transforming the information encoded in a genome into morphological form. To achieve this feat, gene regulatory networks must respond to and integrate environmental signals with their internal dynamics in a robust and coordinated fashion. The highly dynamic nature of this process lends itself to interpretation and analysis in the language of dynamical models. Modelling provides a means of systematically untangling the complicated structure of gene regulatory networks, a framework within which to simulate the behaviour of reconstructed systems and, in some cases, suites of analytic tools for exploring that behaviour and its implications. This review provides a general background to the idea of treating a regulatory network as a dynamical system, and describes a variety of different approaches that have been taken to the dynamical modelling of gene regulatory networks

Core promoters are minimal regions sufficient to direct accurate initiation of transcription and are crucial for regulation of gene expression. They are highly diverse in terms of associated core promoter motifs, underlying sequence composition and patterns of transcription initiation. Distinctive features of promoters are also seen at the chromatin level, including nucleosome positioning patterns and presence of specific histone modifications. Recent advances in identifying and characterizing promoters using next-generation sequencing-based technologies have provided the basis for their classification into functional groups and have shed light on their modes of regulation, with important implications for transcriptional regulation in development. This review discusses the methodology and the results of genome-wide studies that provided insight into the diversity of RNA polymerase II promoter architectures in vertebrates and other Metazoa, and the association of these architectures with distinct modes of regulation in embryonic development and differentiation.

Biological development is a remarkably complex process. A single cell, in an appropriate environment, contains enough information to produce a wide variety of specialised cell types, whose spatial and temporal dynamics interact to form intricately detailed patterns and behaviour. Much of the complexity of a developing system lies in the dynamics of gene regulation that occur within each cell. We used a simple recurrent network to model the process of gene regulation and evolved systems that were able to generate the first four cell divisions of the C. elegans cell lineage tree with a high degree of accuracy

Petal development and senescence entails a normally irreversible process. It starts with petal expansion and pigment production, and ends with nutrient remobilization and ultimately cell death. In many species this is accompanied by petal abscission. Post-harvest stress is an important factor in limiting petal longevity in cut flowers and accelerates some of the processes of senescence such as petal wilting and abscission. However, some of the effects of moderate stress in young flowers are reversible with appropriate treatments. Transcriptomic studies have shown that distinct gene sets are expressed during petal development and senescence. Despite this, the overlap in gene expression between developmental and stress-induced senescence in petals has not been fully investigated in any species. Here a custom-made cDNA microarray from Alstroemeria petals was used to investigate the overlap in gene expression between developmental changes (bud to first sign of senescence) and typical post-harvest stress treatments. Young flowers were stressed by cold or ambient temperatures without water followed by a recovery and rehydration period. Stressed flowers were still at the bud stage after stress treatments. Microarray analysis showed that ambient dehydration stress accelerates many of the changes in gene expression patterns that would normally occur during developmental senescence. However, a higher proportion of gene expression changes in response to cold stress were specific to this stimulus and not senescence related. The expression of 21 transcription factors was characterized, showing that overlapping sets of regulatory genes are activated during developmental senescence and by different stresses

In this thesis I explore what consequences taking development seriously in evolutionary considerations will have for how we understand the evolution of psychology and culture. I first explicate the relationship between development and evolution that informs a number of approaches to evolution, including neo-Darwinian evolutionary biology and evolutionary developmental biology. I argue that, to a greater or lesser extent, developmental processes have been misconstrued in these accounts and that the full role of development, from an evolutionary point of view, has not always been acknowledged. Instead, I suggest that a better model of the relationship between development and evolution can be found in developmental systems theory. I explore the neo-Darwinian underpinnings of a number of accounts of the evolution of culture and psychology, including the branch of evolutionary psychology associated with the work of, among others, John Tooby and Leda Cosmides, and the gene-culture co-evolutionary account of Peter Richerson and Robert Boyd. I argue that as well as being vulnerable to the same sorts of problems that plague neo-Darwinian evolutionary biology, they face other difficulties. These accounts suppose an internalist model of the mind, and this model is neither justified nor useful. The extended mind hypothesis offers a different model of the mind whereby cognitive processes can be partially constituted by structures in the environment. I sketch an alternative account of what the evolution of human psychology and culture by combining a developmental systems approach to evolution and development with the extended mind hypothesis. This will result in a very different understanding of the relationship between biology, psychology and culture

Flowers, serving as the reproductive structures of angiosperms, perform an integral role in plant biology and are fundamental to understanding plant evolution and taxonomy. The growth and organogenesis of flowers are driven by numerous factors, such as external environmental conditions and internal physiological processes, resulting in diverse traits across species or even within the same species. Among these factors, genes play a central role, governing the entire developmental process. The regulation of floral genesis by these genes has become a significant focus of research. In the AE model of floral development, the five structural whorls (calyx, corolla, stamens, pistils, and ovules) are controlled by five groups of genes: A, B, C, D, and E. These genes interact to give rise to a complex control system that governs the floral organsgenesis. The activation or suppression of specific gene categories results in structural modifications to floral organs, with variations observed across different species. The present article examines the regulatory roles of key genes, including genes within the MADS-box and AP2/ERF gene clusters, such as AP1, AP2, AP3, AG, STK, SHP, SEP, PI, and AGL6, as well as other genes, like NAP, SPL, TGA, PAN, and WOX, in shaping floral organ genesis. In addition, it analyzes the molecular-level effects of these genes on floral organ formation. The findings offer a deeper understanding of the genetic governance of floral organ genesis across plant species.

Developmental biology-the study of the processes by which cells, tissues, and organisms develop and change over time-has entered a new golden age. After the molecular genetics revolution in the 80s and 90s and the diversification of the field in the early 21st century, we have entered a phase when powerful technologies provide new approaches and open unexplored avenues. Progress in the field has been accelerated by advances in genomics, imaging, engineering, and computational biology and by emerging model systems ranging from tardigrades to organoids. We summarize how revolutionary technologies have led to remarkable progress in understanding animal development. We describe how classic questions in gene regulation, pattern formation, morphogenesis, organogenesis, and stem cell biology are being revisited. We discuss the connections of development with evolution, self-organization, metabolism, time, and ecology. We speculate how developmental biology might evolve in an era of synthetic biology, artificial intelligence, and human engineering.

Maternal effects, encompassing both genetic (maternally expressed gene products) and non‐genetic (maternal state) influences, are powerful determinants of offspring phenotype, yet their RNA‐level mechanisms remain incompletely resolved. In parallel, epitranscriptomics, an emerging field centered on chemical modifications to RNA, has revealed new layers of gene regulation with implications for cell fate, plasticity, and response to environmental cues. In this perspective article, a conceptual link is proposed between maternal effects and epitranscriptomic mechanisms, focusing on how maternal environments may shape offspring phenotypes through RNA modifications. Evidence is examined from diverse systems, including maternal deposition of modified RNAs, environmental modulation of RNA‐modifying enzymes, and early developmental windows sensitive to maternal inputs. A clear distinction is drawn between placenta‐mediated pathways that reprogram trophoblast/placental epitranscriptomics and direct fetal‐tissue routes that act within developing organs. Although causal demonstrations are still emerging, convergent observations indicate that maternal environments can tune the offspring epitranscriptome with lasting phenotypic consequences. To articulate this emerging connection, the concept of “maternal RNA imprinting” is proposed, the idea that offspring development is shaped by maternal cues via targeted RNA modifications. This article aims not only to synthesize emerging insights across fields but also to stimulate interdisciplinary discussion and encourage investigation into the unexplored intersections of maternal biology and RNA regulation.

Background: Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results: In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T. brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion: Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.Peer reviewe

SNAP25 is an essential SNARE protein for regulated exocytosis in neuronal cells. Differential splicing of the SNAP25 gene results in the expression of two transcripts, SNAP25a and SNAP25b. These splice variants differ by only 9 amino acids, and studies of their expression to date have been limited to analysis of the corresponding mRNAs. Although these studies have been highly informative, it is possible that factors such as differential turnover of the SNAP25 proteins could complicate interpretations based entirely on mRNA expression profiles

Microtubule proteins form a dynamic component of the cytoskeleton, and play key roles in cellular processes, such as vesicular transport, cell motility and mitosis. Expression of microtubule proteins are often dysregulated in cancer. In particular, the microtubule protein βIII-tubulin, encoded by the TUBB3 gene, is aberrantly expressed in a range of epithelial tumours and is associated with drug resistance and aggressive disease. In normal cells, TUBB3 expression is tightly restricted, and is found almost exclusively in neuronal and testicular tissues. Understanding the mechanisms that control TUBB3 expression, both in cancer, mature and developing tissues will help to unravel the basic biology of the protein, its role in cancer, and may ultimately lead to the development of new therapeutic approaches to target this protein. This review is devoted to the transcriptional and posttranscriptional regulation of TUBB3 in normal and cancerous tissue.

The mammalian genome is depleted in CG dinucleotides, except at protected regions where they cluster as CpG islands (CGIs). CGIs are gene regulatory hubs and serve as transcription initiation sites and are as expected, associated with gene promoters. Advances in genomic annotations demonstrate that a quarter of CGIs are found within genes. Such intragenic regions are repressive environments, so it is surprising that CGIs reside here and even more surprising that some resist repression and are transcriptionally active within a gene. Hence, intragenic CGI positioning within genes is not arbitrary and is instead, selected for. As a wealth of recent studies demonstrate, intragenic CGIs are embedded within genes and consequently, influence ‘host’ gene mRNA isoform length and expand transcriptome diversity.

Background A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings Here, we describe a transcriptome-wide analysis of gene expression in tko25tmutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stress-response genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified.Conclusions/Significance These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed

Schizophrenia (SZ) is a devastating mental disorder afflicting 1% of the population. Recent genome-wide association studies (GWASs) of SZ have identified >100 risk loci. However, the causal variants/genes and the causal mechanisms remain largely unknown, which hinders the translation of GWAS findings into disease biology and drug targets. Most risk variants are noncoding, thus likely regulate gene expression. A major mechanism of transcriptional regulation is chromatin remodeling, and open chromatin is a versatile predictor of regulatory sequences. MicroRNA-mediated post-transcriptional regulation plays an important role in SZ pathogenesis. Neurons differentiated from patient-specific induced pluripotent stem cells (iPSCs) provide an experimental model to characterize the genetic perturbation of regulatory variants that are often specific to cell type and/or developmental stage. The emerging genome-editing technology enables the creation of isogenic iPSCs and neurons to efficiently characterize the effects of SZ-associated regulatory variants on SZ-relevant molecular and cellular phenotypes involving dopaminergic, glutamatergic, and GABAergic neurotransmissions. SZ GWAS findings equipped with the emerging functional genomics approaches provide an unprecedented opportunity for understanding new disease biology and identifying novel drug targets.

Draft literature review on approaches to modelling gene regulatory networks