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The UNC-6/netrin pathway plays an important role in cell migration and axon guidance. Ventral sources of UNC-6 guide axons from the ventral to dorsal surface by activating the repulsive UNC-5 receptor and UNC-40 co-receptor, and from dorsal to ventral by activating the attractive UNC-40 receptor. In C. elegans, UNC-129 is a TGF-beta family member expressed in dorsal body wall muscles and is thought to promote the interaction between UNC-5 and UNC-40 for long range repulsion away from ventral sources of UNC-6, while inhibiting UNC-5-alone function. The promotion of UNC-5+UNC-40 signaling could act to increase sensitivity where the UNC-6/netrin concentration is relatively low away from its source. unc-130 encodes a transcription factor that represses expression of unc-129 ventrally. In an unc-130(ev505) mutant, UNC-129 is ectopically expressed, effectively abolishing the gradient of UNC-129 causing migration and axon guidance defects. This project aims to provide better understanding of the UNC-129 pathway by 1) investigating potential UNC-129 receptors and 2) characterizing suppressors of ectopic UNC-129 function. PUR-7 is a candidate UNC-129 receptor discovered in silico that shares similarity to the extracellular domain of canonical TGF-beta receptors. A deletion of genomic DNA that deletes pur-7 and part of the neighbouring srd-4 gene enhances the distal tip cell migration and axon guidance defects of a hypomorphic unc-5 allele, and enhances the migration defects of the unc-130 mutant. Efforts to disentangle the genetic interaction of pur-7 from srd-4 were unfortunately not fruitful. The sup7-2 mutant suppresses distal tip cell migration defects in the unc-130(ev505) mutant, suggesting a role in the UNC-129 pathway. Using mapping and bioinformatical analysis, sup7-2 was located to a genomic region between 5-6 Mb on chromosome X. There are mutations in five candidate genes in this region: ifa-4, tbc-7, gakh-1, actl-1 and C03B1.1. RNAi knockdown of gakh-1 and tbc-7 have an effect on unc-130(ev505) DTC migration defects. Injection of fosmids containing tbc-7 rescue the suppression by sup7-2. Although tbc-7 is likely the sup-7-2 gene, both candidates have an effect on DTC migration and are of interest for future study.
Fundamental Neuroscience, Third Edition introduces graduate and upper-level undergraduate students to the full range of contemporary neuroscience. Addressing instructor and student feedback on the previous edition, all of the chapters are rewritten to make this book more concise and student-friendly than ever before. Each chapter is once again heavily illustrated and provides clinical boxes describing experiments, disorders, and methodological approaches and concepts.Capturing the promise and excitement of this fast-moving field, Fundamental Neuroscience, 3rd Edition is the text that students will be able to reference throughout their neuroscience careers! 30% new material including new chapters on Dendritic Development and Spine Morphogenesis, Chemical Senses, Cerebellum, Eye Movements, Circadian Timing, Sleep and Dreaming, and Consciousness Additional text boxes describing key experiments, disorders, methods, and concepts Multiple model system coverage beyond rats, mice, and monkeys Extensively expanded index for easier referencing
Stem cells have been gaining a lot of attention in recent years. Their unique potential to self-renew and differentiate has turned them into an attractive model for the study of basic biological questions such as cell division, replication, transcription, cell fate decisions, and more. With embryonic stem (ES) cells that can generate each cell type in the mammalian body and adult stem cells that are able to give rise to the cells within a given lineage, basic questions at different developmental stages can be addressed. Importantly, both adult and embryonic stem cells provide an excellent tool for cell therapy, making stem cell research ever more pertinent to regenerative medicine. As the title The Cell Biology of Stem Cells suggests, our book deals with multiple aspects of stem cell biology, ranging from their basic molecular characteristics to the in vivo stem cell trafficking of adult stem cells and the adult stem-cell niche, and ends with a visit to regeneration and cell fate reprogramming. In the first chapter, “Early embryonic cell fate decisions in the mouse”, Amy Ralson and Yojiro Yamanaka describe the mechanisms that support early developmental decisions in the mouse pre-implantation embryo and the current understanding of the source of the most immature stem cell types, which includes ES cells, trophoblast stem (TS) cells and extraembryonic endoderm stem (XEN) cells.
This monograph explores the relationships between cell signaling and the cytoplasmic cytoskeleton in fundamental cell processes, thus bridging the gap between two very active aspects of molecular cell biology. It covers the two main - and reciprocal - questions of these relationships: How are structure and function of the cytoskeleton affected by external signals which impinge on the cell? How does the cytoskeleton influence the cellular signaling processes which determine cell behavior?
The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors. Activation of signaling effectors triggers the release of substances stored in cellular organelles and/or gene transcription and protein synthesis. Complex stages of cell signaling can be studied using proper mathematical models, once the role of each component is carefully handled. Volume 4 also reviews various categories of cytosolic and/or nuclear mediators and illustrates some major signal transduction pathways, such as NFkappaB axis, oxygen sensing, and mechanotransduction.
This first of two volumes provides a general overview of the genetics, structure, mechanism and regulation of the Ras superfamily proteins and describes in detail the signaling pathways and processes regulated by specific members of this family. The focus of this first volume is on the Rho and Ras subfamily of small G proteins. Renowned scientists provide insights into the biochemistry of the classical and non-classical small G-protein family members, their spatio-temporal regulation, their effectors and their roles in health and disease. Together with Volume 2, this book provides a comprehensive and state-of-the-art work on small G-proteins (GTPases). It is intended for graduates and professors in biochemistry and cell biology already working on small G-proteins (small GTPases), but also offers an extremely valuable resource for those readers who are new to the field.