Cold Spring Harbor Perspectives in Biology

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EISSN : 1943-0264
Published by: Cold Spring Harbor Laboratory (10.1101)
Total articles ≅ 1,482
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Carla C. Winter, Zhigang He, Anne Jacobi
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a040923

Abstract:
Axons are a unique cellular structure that allows for the communication between neurons. Axon damage compromises neuronal communications and often leads to functional deficits. Thus, developing strategies that promote effective axon regeneration for functional restoration is highly desirable. One fruitful approach is to dissect the regenerative mechanisms used by some types of neurons in both mammalian and nonmammalian systems that exhibit spontaneous regenerative capacity. Additionally, numerous efforts have been devoted to deciphering the barriers that prevent successful axon regeneration in the most regeneration-refractory system—the adult mammalian central nervous system. As a result, several regeneration-promoting strategies have been developed, but significant limitations remain. This review is aimed to summarize historic progression and current understanding of this exciting yet incomplete endeavor.
Leonid Mirny, Job Dekker
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a040147

Abstract:
Microscopy and genomic approaches provide detailed descriptions of the three-dimensional folding of chromosomes and nuclear organization. The fundamental question is how activity of molecules at the nanometer scale can lead to complex and orchestrated spatial organization at the scale of chromosomes and the whole nucleus. At least three key mechanisms can bridge across scales: (1) tethering of specific loci to nuclear landmarks leads to massive reorganization of the nucleus; (2) spatial compartmentalization of chromatin, which is driven by molecular affinities, results in spatial isolation of active and inactive chromatin; and (3) loop extrusion activity of SMC (structural maintenance of chromosome) complexes can explain many features of interphase chromatin folding and underlies key phenomena during mitosis. Interestingly, many features of chromosome organization ultimately result from collective action and the interplay between these mechanisms, and are further modulated by transcription and topological constraints. Finally, we highlight some outstanding questions that are critical for our understanding of nuclear organization and function. We believe many of these questions can be answered in the coming years.
Peter W. Reddien
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a040717

Abstract:
The capacity for regeneration is broad in the animal kingdom. Planarians are flatworms that can regenerate any missing body part and their regenerative powers have combined with ease of experimentation to make them a classic regeneration model for more than a century. Pluripotent stem cells called neoblasts generate missing planarian tissues. Fate specification happens in the neoblasts, and this can occur in response to regeneration instructions in the form of positional information. Fate specification can lead to differentiating cells in single steps rather than requiring a long lineage hierarchy. Planarians display constitutive expression of positional information from muscle cells, which is required for patterned maintenance of tissues in tissue turnover. Amputation leads to the rapid resetting of positional information in a process triggered by wound signaling and the resetting of positional information is required for regeneration. These findings suggest a model for planarian regeneration in which adult positional information resets after injury to regulate stem cells to bring about the replacement of missing parts.
Elizabeth S. Williams, Michelle Mazei-Robison, A.J. Robison
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a039198

Abstract:
Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.
Sofia A. Quinodoz, Mitchell Guttman
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a039719

Abstract:
It has long been proposed that nuclear RNAs might play an important role in organizing the structure of the nucleus. Initial experiments performed more than 30 years ago found that global disruption of RNA led to visible rearrangements of nuclear organization. Yet, this idea remained controversial for many years, in large part because it was unclear what specific RNAs might be involved, and which specific nuclear structures might be dependent on RNA. Over the past few years, the contributions of RNA to organizing nuclear structures have become clearer with the discovery that many nuclear bodies are enriched for specific noncoding RNAs (ncRNAs); in specific cases, ncRNAs have been shown to be essential for establishment and maintenance of these nuclear structures. More recently, many different ncRNAs have been shown to play critical roles in initiating the three-dimensional (3D) spatial organization of DNA, RNA, and protein molecules in the nucleus. These examples, combined with global imaging and genomic experiments, have begun to paint a picture of a broader role for RNA in nuclear organization and to uncover a unifying mechanism that may explain why RNA is a uniquely suited molecule for this role. In this review, we provide an overview of the history of RNA and nuclear structure and discuss key examples of RNA-mediated bodies, the global roles of ncRNAs in shaping nuclear structure, and emerging insights into mechanisms of RNA-mediated nuclear organization.
Zhenhai Du, Ke Zhang, Wei Xie
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a039677

Abstract:
Dramatic nuclear reorganization occurs during early development to convert terminally differentiated gametes to a totipotent zygote, which then gives rise to an embryo. Aberrant epigenome resetting severely impairs embryo development and even leads to lethality. How the epigenomes are inherited, reprogrammed, and reestablished in this critical developmental period has gradually been unveiled through the rapid development of technologies including ultrasensitive chromatin analysis methods. In this review, we summarize the latest findings on epigenetic reprogramming in gametogenesis and embryogenesis, and how it contributes to gamete maturation and parental-to-zygotic transition. Finally, we highlight the key questions that remain to be answered to fully understand chromatin regulation and nuclear reprogramming in early development.
Xianrong Wong, Ashley J. Melendez-Perez, Karen L. Reddy
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a040113

Abstract:
Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself to form a nuclear subcompartment, the nuclear lamina, that is involved in a variety of cellular processes such as the governance of nuclear integrity, nuclear positioning, mitosis, DNA repair, DNA replication, splicing, signaling, mechanotransduction and -sensation, transcriptional regulation, and genome organization. Lamins are the primary scaffold for this nuclear subcompartment, but interactions with lamin-associated peptides in the inner nuclear membrane are self-reinforcing and mutually required. Lamins also interact, directly and indirectly, with peripheral heterochromatin domains called lamina-associated domains (LADs) and help to regulate dynamic 3D genome organization and expression of developmentally regulated genes.
Asli Yildirim, Lorenzo Boninsegna, Yuxiang Zhan, Frank Alber
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a039693

Abstract:
Our understanding of how genomic DNA is tightly packed inside the nucleus, yet is still accessible for vital cellular processes, has grown dramatically over recent years with advances in microscopy and genomics technologies. Computational methods have played a pivotal role in the structural interpretation of experimental data, which helped unravel some organizational principles of genome folding. Here, we give an overview of current computational efforts in mechanistic and data-driven 3D chromatin structure modeling. We discuss strengths and limitations of different methods and evaluate the added value and benefits of computational approaches to infer the 3D structural and dynamic properties of the genome and its underlying mechanisms at different scales and resolution, ranging from the dynamic formation of chromatin loops and topological associated domains to nuclear compartmentalization of chromatin and nuclear bodies.
Jiří Friml
Cold Spring Harbor Perspectives in Biology; https://doi.org/10.1101/cshperspect.a039859

Abstract:
Auxin has always been at the forefront of research in plant physiology and development. Since the earliest contemplations by Julius von Sachs and Charles Darwin, more than a century-long struggle has been waged to understand its function. This largely reflects the failures, successes, and inevitable progress in the entire field of plant signaling and development. Here I present 14 stations on our long and sometimes mystical journey to understand auxin. These highlights were selected to give a flavor of the field and to show the scope and limits of our current knowledge. A special focus is put on features that make auxin unique among phytohormones, such as its dynamic, directional transport network, which integrates external and internal signals, including self-organizing feedback. Accented are persistent mysteries and controversies. The unexpected discoveries related to rapid auxin responses and growth regulation recently disturbed our contentment regarding understanding of the auxin signaling mechanism. These new revelations, along with advances in technology, usher us into a new, exciting era in auxin research.
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