Annual review of cell and developmental biology最新文献

How cells diversify to form an embryo represents a profound interdisciplinary challenge. Decades of innovative research using model organisms have uncovered principles of lineage specification, morphogenesis, epigenetic mechanisms, and gene regulation that underlie this fundamental process. As biology enters the genomic era, marked by rapid convergence of technological and computational advances, construction of quantitative and heuristic models of development becomes increasingly feasible. In gastrulation, a founding population of equipotent stem cells rapidly diversifies in a highly canonical manner to form the basic body plan. This review discusses considerations required to establish a time-resolved model that reflects the cellular and molecular aspects involved in this process. Building on insights from recent studies and the transformative potential of evolving technologies and experimental frameworks, we discuss how to devise such a model by integrating multiple molecular modalities at the single-cell level within the spatial context as a benchmark for studying cell specification.

The primordial body architecture of vertebrates is established during gastrulation, a critical period of development characterized by the emergence of the three germ layers (ectoderm, mesoderm, and endoderm) and the formation of an embryo with clearly identifiable dorso-ventral and anterior-posterior axes. In zebrafish, gastrulation involves molecular and cellular mechanisms that are broadly conserved among vertebrates, with species-specific features imposed by the deterministic role of maternally deposited determinants, the architecture of extraembryonic structures that create a dynamic and physically constrained environment, and the mesenchymal nature of early cells that underpins the migratory nature of mesendoderm internalization. Significant progress has been made in the genetic networks, signaling pathways, and cell dynamics involved, and the unique features of the zebrafish embryo are helping to elucidate the intricate coordination between gene expression, mechanical forces, self-organization, and morphogenetic movements that shape the early embryo. These advances have provided insights into the fundamental principles of vertebrate morphogenesis.

Bioelectricity is likely as old as life itself. From the moment the first proto-cell was enclosed in a lipid bilayer, a membrane potential arose. Thus, one can expect that bioelectrical activities influence single-cell and collective cell behaviors in processes such as embryo development, tissue repair, and even disease. Despite the ubiquity of bioelectrical phenomena, most research has focused on bioelectrical control of neural tissues, and as a result, our knowledge of nonneural contexts remains comparatively less understood, scattered, and often misunderstood. Still, there are strong reasons for supporting the idea that bioelectricity contributes to diverse morphogenetic contexts. Thus, in this review we provide an overview of the current knowledge of how cells generate and perceive bioelectrical inputs, and discuss how cells translate these stimuli into responses that influence tissue morphogenesis in physiology and pathology.

The hippocampus is critical for an array of cognitive functions arising from its complex substructure and connectivity. Important insights into hippocampal field specification emerged from classical studies that examined mice lacking particular transcription factors or signaling molecules. Recent high-throughput bioinformatics approaches have led to fresh perspectives on these findings. This review offers a semihistorical timeline of the discovery of the hippocampal organizer and examines the interplay of factors that position this structure. We compare the rich body of literature in the mouse with studies in nonmammalian vertebrates and in human-derived organoid models that reveal commonalities in the mechanisms that induce specific hippocampal fates. We also examine the regulation of neurogenesis versus gliogenesis and the migration of different cell types in the hippocampus. We discuss open questions that arise from discoveries made over the past three decades, and suggest hypotheses or approaches that will expand our understanding of the choreography of hippocampal development.

Cellular cannibalism, defined as one cell eating another, is a widespread cellular behavior in organisms ranging from flies and worms to fish and mammals, where it is essential for development and homeostasis. Some cells nibble on other cells in a process called trogocytosis or grooming. Alternatively, cells can engulf other cells whole, as when macrophages consume stressed stem cells or aged red blood cells. Excessive cellular cannibalism can lead to degenerative disease or immunodeficiency, and cancer cells can hijack this normal behavior to fuel their growth and evade immune attack. Next-generation immunotherapies aim to harness cannibalistic behavior to combat cancer and other diseases, including atherosclerosis. Chimeric antigen receptor macrophage (CAR-M) therapies are in clinical trials for cancer. Elucidating the molecular and cellular mechanisms that drive physiological and pathological cellular cannibalism is likely to inform efforts to improve CAR-M and other therapies that depend on antibody-dependent cellular phagocytosis and tumor-associated macrophage reprogramming.

The RNA exosome is a conserved multiprotein complex essential for 3'-to-5' RNA degradation in eukaryotic cells. In the cytoplasm, the exosome participates in messenger RNA surveillance and decay, while in the nucleus and nucleolus it performs a broader range of functions, from fully degrading cryptic RNAs generated by faulty or pervasive transcription to precisely trimming structured RNAs. An extended network of obligate cofactors and transient RNA helicase complexes has evolved to handle the large variety of substrates in each subcellular compartment. This network organizes in layers around the exosome core and regulates the irreversible 3'-to-5' degradative action in synergy with the features of the substrates. In this review, we discuss findings derived from genetic, cellular, biochemical, and structural analyses of nuclear and cytoplasmic exosome complexes, and integrate them into molecular movies that illustrate the mechanistic principles of this versatile and dynamic machine in RNA processing and RNA decay.

Science is often portrayed as the objective search for knowledge. However, science is also part of complex societies that shape science and in turn are shaped by scientific findings. In this interview, Bruce Alberts, former president of the US National Academy of Sciences, and Paul Nurse, former and future president of the Royal Society, discuss the roles of science and scientists in society. They share their passion to understand the natural world and the joy of discovery. They emphasize the importance of leadership in building institutions that support science and evidence-based decision-making. They share their frustration that current science education falls short in teaching the way science arrives at a better but incomplete understanding of the world. They urge scientists to organize and make their case to the public and fight misinformation and mistruths.

Root nodule symbiosis allows for plant acquisition of reactive nitrogen through fixation of atmospheric molecular dinitrogen by nitrogen-fixing bacteria. Nodulation is a complex trait, with diverse modes of bacterial infection and nodule morphologies across species, reflecting evolutionary adaptation. Understanding ancient forms of this trait may carry advantages for its current utilization, since basal states likely reflect the least complexity. In this review we focus on the evolution of nodule development, particularly on events that have led to increased complexity of this symbiosis in later adaptations. We hypothesize that the ancestral form of nodulation comprises an evolutionary coupling of nutrient-dependent lateral root development with apoplastic intercellular bacterial growth, alongside the acquisition or evolution of an ancestral chitinaceous signaling molecule by the microbial symbiont. Uncovering the evolutionary adaptations underpinning the extant diversity of this trait allows for a better understanding of the simplest ancestral state.

Stem cells are undifferentiated cells capable of self-renewal and differentiation into specialized cell types, forming the foundation of tissue maintenance and repair. In the blood system, this process is known as hematopoiesis. Hematopoietic stem cells (HSCs), positioned at the apex of the hematopoietic hierarchy, have the unique ability to reconstitute the hematopoietic system long-term. HSC stemness is defined by multipotency, allowing differentiation into all blood lineages, and self-renewal, maintaining the stem cell pool. A fundamental property of HSCs is quiescence, which refers to a reversible inactive cell cycle state that preserves their self-renewal potential. Dormant HSCs represent a subset of quiescent stem cells with minimal division rates and the most potent stemness. Dysregulation of dormancy and quiescence is linked to HSC dysfunction. Here, we explore mechanisms regulating HSC dormancy and quiescence under homeostatic and stress conditions. Finally, we describe how factors such as aging, inflammation, and malignancies disrupt these states.

Cells must constantly adapt their metabolism to the availability of nutrients and signals from their environment. Under conditions of limited nutrients, cells need to reprogram their metabolism to rely on internal stores of glucose and lipid metabolites. From the emergence of eukaryotes to the mitochondria as the central source of ATP and other metabolites required for cellular homeostasis, survival, and proliferation, cells had to evolve sensors to detect even modest changes in mitochondrial function in order to safeguard cellular integrity and prevent energetic catastrophe. Homologs of AMP-activated protein kinase (AMPK) are found in all eukaryotic species and serve as an ancient sensor of conditions of low cellular energy. Here we explore advances in how AMPK modulates core processes underpinning the mitochondrial life cycle and how it serves to restore mitochondrial health in parallel with other beneficial metabolic adaptations.