Cold Spring Harbor perspectives in biology最新文献

As cells migrate inside the body, they encounter various biochemical and physical cues that provide them with directional guidance. In the past 20 years or so, there has been a significant shift in the effort to understand how physical factors contribute to cellular behaviors. Nevertheless, much of the research has been focused on the interactions between migrating cells and the extracellular matrix in vitro as these are simpler and more accessible models, while neglecting the importance of the cellular environment, which often requires in vivo model systems. With the development of new technology along with the appropriate choice of model organisms, the interesting topic of cell-on-cell interaction during migration is beginning to unravel. In this review, we will take a deep dive into some of the recent results that demonstrate how the biophysics of the cellular environment can impact cell migration, with a strong focus on the use of in vivo model systems, naming the Drosophila border cells, the Xenopus cephalic neural crest, and the zebrafish posterior lateral line primordium.

Blood vessels are critical to deliver oxygen and nutrients to tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier (BBB), which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and protects the neural tissue from toxins and pathogens, and alterations of this barrier are important components of the pathogenesis and progression of various neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the brain endothelial cells (ECs) that form the walls of the blood vessels. These properties are regulated by interactions between different vascular, perivascular, immune, and neural cells. Understanding how these cell populations interact to regulate barrier properties is essential for understanding how the brain functions in both health and disease contexts.

Skeletal muscle is one of the tissues with the highest range of variability in metabolic rate, which, to a large extent, is critically dependent on tightly controlled and fine-tuned mitochondrial activity. Besides energy production, other mitochondrial processes, including calcium buffering, generation of heat, redox and reactive oxygen species homeostasis, intermediate metabolism, substrate biosynthesis, and anaplerosis, are essential for proper muscle contractility and performance. It is thus not surprising that adequate mitochondrial function is ensured by a plethora of mechanisms, aimed at balancing mitochondrial biogenesis, proteostasis, dynamics, and degradation. The fine-tuning of such maintenance mechanisms ranges from proper folding or degradation of individual proteins to the elimination of whole organelles, and in extremis, apoptosis of cells. In this review, the present knowledge on these processes in the context of skeletal muscle biology is summarized. Moreover, existing gaps in knowledge are highlighted, alluding to potential future studies and therapeutic implications.

Neuronal circuits represent the functional units of the brain. Understanding how the circuits are generated to perform computations will help us understand how the brain functions. Nevertheless, neuronal circuits are not engineered, but have formed through millions of years of animal evolution. We posit that it is necessary to study neuronal circuit evolution to comprehensively understand circuit function. Here, we review our current knowledge regarding the mechanisms that underlie circuit evolution. First, we describe the possible genetic and developmental mechanisms that have contributed to circuit evolution. Then, we discuss the structural changes of circuits during evolution and how these changes affected circuit function. Finally, we try to put circuit evolution in an ecological context and assess the adaptive significance of specific examples. We argue that, thanks to the advent of new tools and technologies, evolutionary neurobiology now allows us to address questions regarding the evolution of circuitry and behavior that were unimaginable until very recently.

The blastocyst forms during the first days of mammalian development. The structure of the blastocyst is conserved among placental mammals and is paramount to the establishment of the first mammalian lineages. The blastocyst is composed of an extraembryonic epithelium, the trophectoderm (TE), that envelopes a fluid-filled lumen and the inner cell mass (ICM). To shape the blastocyst, embryos transit through three stages driven by forces that have been characterized in the mouse embryo over the past decade. The morphogenetically quiescent cleavage stages mask dynamic cytoskeletal remodeling. Then, during the formation of the morula, cells pull themselves together and the strongest ones internalize. Finally, the blastocyst forms after the pressurized lumen breaks the radial symmetry of the embryo before expanding in cycles of collapses and regrowth. In this review, we delineate the force patterns sculpting the blastocyst, based on our knowledge on the mouse and, to some extent, human embryos.

Saccharomyces cerevisiae, a model organism in telomere biology, has been instrumental in pioneering a comprehensive understanding of the molecular processes that occur in the absence of telomerase across eukaryotes. This exploration spans investigations into telomere dynamics, intracellular signaling cascades, and organelle-mediated responses, elucidating their impact on proliferative capacity, genome stability, and cellular variability. Through the lens of budding yeast, numerous sources of cellular heterogeneity have been identified, dissected, and modeled, shedding light on the risks associated with telomeric state transitions, including the evasion of senescence. Moreover, the unraveling of the intricate interplay between the nucleus and other organelles upon telomerase inactivation has provided insights into eukaryotic evolution and cellular communication networks. These contributions, akin to milestones achieved using budding yeast, such as the discovery of the cell cycle, DNA damage checkpoint mechanisms, and DNA replication and repair processes, have been of paramount significance for the telomere field. Particularly, these insights extend to understanding replicative senescence as an anticancer mechanism in humans and enhancing our understanding of eukaryotes' evolution.

Telomerase ribonucleoprotein (RNP) plays a crucial role in maintaining telomere length by processively adding telomeric repeats to the 3' ends of chromosomes. Telomerase activation is linked to cancer, while mutations that compromise telomerase function result in diseases such as dyskeratosis congenita. The synthesis of telomeric repeats necessitates two core telomerase components: telomerase reverse transcriptase (TERT) and telomerase RNA (TER). However, cellular telomerase holoenzymes encompass a diverse range of protein factors, both constitutively and transiently interacting. These factors are integral to telomerase assembly or regulation at telomeres. This review emphasizes recent advancements in structural studies of telomerase holoenzymes and their associated factors from Tetrahymena thermophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and humans. These studies have significantly deepened our molecular understanding not only of the mechanism underlying telomeric repeat synthesis but also of the biological roles of telomerase-associated proteins.

Telomerase is a large ribonucleoprotein complex responsible for the addition of telomeric DNA repeats to chromosomal ends. Telomerase is composed of core and accessory components that work in coordination to ensure telomere length is maintained during development and in specific cell types. Telomerase activity is tightly regulated and is strongly increased in most tumor cells. On the other hand, loss-of-function mutations either in accessory factors or in core components of the complex impact telomere maintenance and cause a large spectrum of severe phenotypes, typically described as telomere biology disorders. A central element for efficient telomerase function is the proper biogenesis and assembly of the holoenzyme. Here, we discuss our current understanding of these processes and how they modulate telomerase efficiency. We consider how these processes are influenced by the specific subcellular localization of different telomerase components during different stages of the assembly of the holoenzyme. We describe the tremendous progress made in this area over the last decade and how recently discovered aspects of telomerase biogenesis can be exploited clinically, to actively benefit patients suffering from telomere biology disorders.

Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how telomeric shortening in specific tissues can unleash widespread organ dysfunction and disease. This highlights a novel aspect of tissue communication, whereby telomere shortening in one organ can propagate through biological networks, influencing the aging process systemically. These discoveries position zebrafish as a valuable model for studying the complex interactions between telomeres, aging, and tissue cross talk, providing important insights with direct relevance to human health and longevity.

Two things about Mendel were "rediscovered" in 1900: His famous paper of 1865 and the story of his life and long neglect. Unlike the paper, which anyone could read in its entirety, the story came out only gradually, and many of its elements were misconstrued by Western European scientists. They pictured him as a pure scientist like themselves and were puzzled by or disinterested in his career as a clergyman, his intellectual community in far-off Moravia, and the importance to him of practical plant breeding. This paper recapitulates the process of mythmaking that followed the rediscovery, then shows how more recent historical research has been able to undo it and, in a sense, "unrediscover" Mendel.