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Determination of left–right asymmetry in mouse embryos is achieved by a leftward fluid flow (nodal flow) in the node cavity that is generated by clockwise rotational movement of 200–300 cilia in the node. The precise action of nodal flow and how much flow input is required for the robust read-out of left–right determination remains unknown. Here we show that a local leftward flow generated by as few as two rotating cilia is sufficient to break left–right symmetry. Quantitative analysis of fluid flow and ciliary rotation in the node of mouse embryos shows that left–right asymmetry is already established within a few hours after the onset of rotation by a subset of nodal cilia. Examination of various ciliary mutant mice shows that two rotating cilia are sufficient to initiate left–right asymmetric gene expression. Our results suggest the existence of a highly sensitive system in the node that is able to sense an extremely weak unidirectional flow, and may favour a model in which the flow is sensed as a mechanical force. The left–right asymmetry of an organism is patterned during development and is determined by fluid flow created by the movement of cilia. In this study, the asymmetry is shown to be determined early after the movement of cilia is established and that only two rotating cilia are required for breaking symmetry.

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development. This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved.

In light sheet–based fluorescence microscopy (LSFM), optical sectioning in the excitation process minimizes fluorophore bleaching and phototoxic effects. Because biological specimens survive long-term three-dimensional imaging at high spatiotemporal resolution, LSFM has become the tool of choice in developmental biology.

Key Points Developmental symbiosis and developmental plasticity contribute in numerous ways to animal evolution Symbionts help to generate organs and maintain species-specific interactions with their animal hosts. Symbionts provide selectable variation and can generate the conditions for reproductive isolation Symbionts may have promoted major evolutionary transitions such as multicellularity Plasticity allows the integration of the organism into its environment, changing development to account for predators, conspecifics, diet and temperature. Plasticity provides the raw material for genetic accommodation and niche construction. Plasticity can both help and harm populations experiencing stresses such as global climate change. Ecological evolutionary developmental biology (Eco-Evo-Devo) is a relatively new field that integrates developmental biology and ecology into evolutionary theory. The authors review new research in this field relating to the roles of developmental plasticity and developmental symbiosis in evolution. The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.

Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses. Finally, ExM could resolve subsynaptic protein organization, such as ring-like structures composed of glycine receptors. Regarding development, we used ExM to characterize the shapes of nuclear invaginations and channels, and to visualize cytoskeletal proteins nearby. We detected nuclear invagination channels at late prophase and telophase, potentially suggesting roles for such channels in cell division. Thus, ExM of the larval and embryonic zebrafish may enable systematic studies of how molecular components are configured in multiple contexts of interest to neuroscience and developmental biology.

Developmental biology has been continually shaped by technological advances, evolving from a descriptive science into one immersed in molecular and cellular mechanisms. Most recently, genome sequencing and 'omics' profiling have provided developmental biologists with a wealth of genetic and biochemical information; however, fully translating this knowledge into functional understanding will require new experimental capabilities. Photoactivatable probes have emerged as particularly valuable tools for investigating developmental mechanisms, as they can enable rapid, specific manipulations of DNA, RNA, proteins, and cells with spatiotemporal precision. In this Perspective, we describe optochemical and optogenetic systems that have been applied in multicellular organisms, insights gained through the use of these probes, and their current limitations. We also suggest how chemical biologists can expand the reach of photoactivatable technologies and bring new depth to our understanding of organismal development.

Key Points Quantitative approaches are used increasingly in evolutionary developmental biology ('evo-devo'). In particular, geometric morphometrics is widely used to quantify the shape of organisms or their parts. A wide range of tools is available to address specific questions and interpret results in their anatomical context. Genetic studies of shape variation have shown that inheritance tends to be polygenic, with many loci of mostly small effects. Because developmental processes integrate variation from diverse sources, interactions of genes with each other and with environmental factors seem to be important. Shape variation tends to be integrated and often has a modular structure; there is usually strong integration within morphological modules but relatively weak integration among modules. Strong integration can act as an evolutionary constraint by hindering the independent evolution of different traits. Identifying constraints and their evolutionary effects is an active area of current research. Functional considerations are increasingly important in evo-devo and provide explicit links between the genetic and developmental basis of variation and its adaptive significance for evolving populations. Large-scale comparative analyses of shape with an explicit phylogenetic basis provide a means of examining the long-term evolutionary consequences of the processes observed in contemporary populations. Overall, integration of quantitative approaches into evo-devo promises to unify developmental and adaptive factors of morphological evolution. Evolutionary developmental biology is being advanced by quantitative methods for studying morphology. This Review considers such approaches and emerging insights into interactions between genetic and non-genetic factors, as well as the evolutionary constraints that influence shape. Morphological traits have long been a focus of evolutionary developmental biology ('evo-devo'), but new methods for quantifying shape variation are opening unprecedented possibilities for investigating the developmental basis of evolutionary change. Morphometric analyses are revealing that development mediates complex interactions between genetic and environmental factors affecting shape. Evolution results from changes in those interactions, as natural selection favours shapes that more effectively perform some fitness-related functions. Quantitative studies of shape can characterize developmental and genetic effects and discover their relative importance. They integrate evo-devo and related disciplines into a coherent understanding of evolutionary processes from populations to large-scale evolutionary radiations.

Key Points Methods for tracing lineage can be divided into two groups. Prospective methods trace lineage forwards from the application of an experimentally delivered marker, and retrospective methods trace lineage backwards, using endogenous marks that naturally accumulate in the genome. Early methods using sparse retroviral labelling for prospective lineage tracing have given way to retroviral barcodes of essentially unlimited complexity, allowing the labelling and recovery of large populations of cells for lineage tracing experiments. Genetic recombination with Cre- loxP or engineered transposon systems is a popular method for lineage tracing in genetically accessible model organisms. Recent work has demonstrated that CRISPR–Cas9 genome editing is a promising way to track and synthetically reconstruct cell lineage relationships in complex multicellular organisms, and may supplement or supplant older recombination-based systems in the future. Recent advances in single-cell genome amplification and sequencing make it possible to harness naturally occurring somatic mutations to infer cell lineage information retrospectively. Somatic mutations of many classes, including long interspersed nuclear element 1 (L1; also known as LINE-1) retrotransposition events, copy-number variants, single-nucleotide variants and microsatellite length variants, are appropriate for lineage tracing. Single-cell genome-sequencing experiments require genome amplification, and investigators must consider the frequencies and types of errors that are introduced by different amplification methods to select an approach that best balances signal and noise for the experiment at hand. When designing a lineage tracing experiment, it is important to consider the strengths and weaknesses of either a prospective or a retrospective approach. Prospective approaches require genetic access to the cell population being labelled, but can often be higher throughput and less expensive than retrospective approaches. Retrospective approaches use marks that accumulate in the genome, making any purifiable population accessible to analysis, but can be low-throughput and expensive. Lineage analyses of multicellular organisms provide key insights into developmental mechanisms and how these developmental trajectories go awry in diverse diseases. This Review discusses the features, technical challenges and latest opportunities of an evolving range of sophisticated genetic techniques for tracking cell lineages in organisms. These strategies include methods for prospective tracking using engineered genetic constructs, as well as retrospective tracking based on naturally occurring somatic mutations. Resolving lineage relationships between cells in an organism is a fundamental interest of developmental biology. Furthermore, investigating lineage can drive understanding of pathological states, including cancer, as well as understanding of developmental pathways that are amenable to manipulation by directed differentiation. Although lineage tracking through the injection of retroviral libraries has long been the state of the art, a recent explosion of methodological advances in exogenous labelling and single-cell sequencing have enabled lineage tracking at larger scales, in more detail, and in a wider range of species than was previously considered possible. In this Review, we discuss these techniques for cell lineage tracking, with attention both to those that trace lineage forwards from experimental labelling, and those that trace backwards across the life history of an organism.

The dynamic and meticulously regulated networks established the foundation for embryonic development, where the intercellular interactions and signal transduction assumed a pivotal role. In recent years, high-throughput technologies such as single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have advanced dramatically, empowering the systematic dissection of cell-to-cell regulatory networks. The emergence of comprehensive databases and analytical frameworks has further provided unprecedented insights into embryonic development and cell–cell interactions (CCIs). This paper reviewed the exponential increased CCIs works related to developmental biology from 2008 to 2023, comprehensively collected and categorized 93 analytical tools and 39 databases, and demonstrated its practical utility through illustrative case studies. In parallel, the article critically scrutinized the persistent challenges within this field, such as the intricacies of spatial localization and transmembrane state validation at single-cell resolution, and underscored the interpretative limitations inherent in current analytical frameworks. The development of CCIs’ analysis tools with harmonizing multi-omics data and the construction of cross-species dynamically updated CCIs databases will be the main direction of future research. Future investigations into CCIs are poised to expeditiously drive the application and clinical translation within developmental biology, unlocking novel dimensions for exploration and progress.

Matrix-assisted laser desorption/ionization ( MALDI ) imaging mass spectrometry (IMS) is emerging as a powerful tool for investigating the distribution of molecules within biological systems through the direct analysis of thin tissue sections. Unique among imaging methods, MALDI -IMS can determine the distribution of hundreds of unknown compounds in a single measurement. We discuss the current state of the art of MALDI -IMS along with some recent applications and technological developments that illustrate not only its current capabilities but also the future potential of the technique to provide a better understanding of the underlying molecular mechanisms of biological processes.