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Developmental pattern formation is orchestrated by diffusible signaling molecules, termed morphogens, that form gradients from which cells can determine positionally appropriate fates. Stochasticity in morphogen binding, signal transduction, and gene expression create local cell-to-cell variability in the readout of morphogen gradients. However, little is known about the actual levels of noise in morphogen gradient responses, or the mechanisms that might control it. To investigate this, I quantified the transcriptional activity noise, protein expression noise, and protein half-life of optomotor blind (omb), one of the downstream targets of the morphogen Dpp in the Drosophila larval wing imaginal disc. Using combined fluorescence in situ hybridization (FISH) with intronic probes, immunofluorescence, image segmentation and image analysis, I observed a very high level of transcriptional variability characterized by coefficients of variation (CV) as high as ~110%, in the cells in which omb plays a central role in specifying the location of wing vein primordium L5. However, the half-life of the Omb protein was found to be very long, ~ 6 hours, which would be expected to provide significant temporal filtering of the transcriptional noise. I showed that the reduction in noise from transcript to protein is sufficient to account for the precision of the positional information that patterns vein L5. I also investigated why the positioning of vein L5 is remarkably robust to genetic manipulation that change the shape of the Dpp morphogen gradient. I observed that patters of Dpp signaling and Omb expression are not constant during larval development, but change continuously, and not always in concert with each other. By taking into account the long half-life of Omb it was possible to build a model that explains both these movements and the remarkable robustness of L5 patterning to changes in Dpp gradient shape.
Gradients and Tissue Patterning, Volume 137 in the Current Topics in Developmental Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics. Each chapter is written by an international board of authors.
Signalling by morphogens such as the Hedgehog family, Notch, Wingless/Wnt and various growth factors is essential during embryogenesis. The establishment of concentration gradients of these morphogens plays a key role during developmental patterning in all multicellular organisms, assuring that distinct cell/tissue types and organs appear at the right place in the right time during embryogenesis. Regulation of morphogen synthesis, trafficking and diffusion are all known to play a part in setting up these gradients, and a complex web of signaling mechanisms ensures that specific responses occur at the correct threshold concentration in the recipient cells whose fate depends on these morphogens.
The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development and on new psychiatric/neurological treatments being developed based on our increased understanding of developmental mechanisms. Each volume in the series consists of review style articles that average 15-20pp and feature numerous illustrations and full references. Volume 1 offers 48 high level articles devoted mainly to patterning and cell type specification in the developing central and peripheral nervous systems. Series offers 144 articles for 2904 full color pages addressing ways in which the nervous system and its components develop Features leading experts in various subfields as Section Editors and article Authors All articles peer reviewed by Section Editors to ensure accuracy, thoroughness, and scholarship Volume 1 sections include coverage of mechanisms which: control regional specification, regulate proliferation of neuronal progenitors and control differentiation and survival of specific neuronal subtypes, and controlling development of non-neural cells
Cell Polarity in Development and Disease offers insights into the basic molecular mechanisms of common diseases that arise as a result of a loss of ordered organization and intrinsic polarity. Included are diseases affecting highly polarized epithelial tissues in the lung and kidney, as well as loss and gain of cell polarity in the onset and progression of cancer. This book provides a basic resource for understanding the biology of polarity, offering a starting point for those thinking of targeting cell polarity for translational medical research. Provides basic science understanding of cell polarity disease and development Covers diseases affecting polarized epithelial tissues in the lung and kidney, also covering the progression of cancer Includes historical context of cell polarity research for potential future breakthroughs
A survey of how engineering techniques from control and systems theory can be used to help biologists understand the behavior of cellular systems.
The greatest mystery of life is how a single fertilized egg develops into a fully functioning, sometimes conscious multicellular organism. Embryogenesis Explained offers a new theory of how embryos build themselves, and combines simple physics with the most recent biochemical and genetic breakthroughs, based on the authors' prediction and then discovery of differentiation waves. They explain their ideas in a form accessible to the lay person and a broad spectrum of scientists and engineers. The diverse subjects of development, genetics and evolution, and their physics, are brought together to explain this major, previously unanswered scientific question of our time.As a follow up on The Hierarchical Genome, this book is a shorter but conceptually expanded work for the reader who is interested in science. It is useful as a starting point for the curious layman or the scientist or professional encountering the problem of embryogenesis without the formal biology background. There is also material useful for the seasoned biologist caught up in the new rush of information about the role of mechanics in developmental biology and cellular level mechanics in medicine.
Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.
A physicist's guide to the phenomena of life Interactions between the fields of physics and biology reach back over a century, and some of the most significant developments in biology—from the discovery of DNA's structure to imaging of the human brain—have involved collaboration across this disciplinary boundary. For a new generation of physicists, the phenomena of life pose exciting challenges to physics itself, and biophysics has emerged as an important subfield of this discipline. Here, William Bialek provides the first graduate-level introduction to biophysics aimed at physics students. Bialek begins by exploring how photon counting in vision offers important lessons about the opportunities for quantitative, physics-style experiments on diverse biological phenomena. He draws from these lessons three general physical principles—the importance of noise, the need to understand the extraordinary performance of living systems without appealing to finely tuned parameters, and the critical role of the representation and flow of information in the business of life. Bialek then applies these principles to a broad range of phenomena, including the control of gene expression, perception and memory, protein folding, the mechanics of the inner ear, the dynamics of biochemical reactions, and pattern formation in developing embryos. Featuring numerous problems and exercises throughout, Biophysics emphasizes the unifying power of abstract physical principles to motivate new and novel experiments on biological systems. Covers a range of biological phenomena from the physicist's perspective Features 200 problems Draws on statistical mechanics, quantum mechanics, and related mathematical concepts Includes an annotated bibliography and detailed appendixes