Developmental and stem cell biology's bright future.

The next 50 years of developmental biology will illuminate exciting new discoveries but are also poised to provide solutions to important problems society faces. Ten scientists whose work intersects with developmental biology in various capacities tell us about their vision for the future.

Modelling post-implantation human development to yolk sac blood emergence.

Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system1,2. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons3-5. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage6-16. Here we present a genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis that captures the reciprocal codevelopment of embryonic tissue and the extra-embryonic endoderm and mesoderm niche with early haematopoiesis. This model is produced from induced pluripotent stem cells and shows unanticipated self-organizing cellular programmes similar to those that occur in embryogenesis, including the formation of amniotic cavity and bilaminar disc morphologies as well as the generation of an anterior hypoblast pole and posterior domain. The extra-embryonic layer in these embryoids lacks trophoblast and shows advanced multilineage yolk sac tissue-like morphogenesis that harbours a process similar to distinct waves of haematopoiesis, including the emergence of erythroid-, megakaryocyte-, myeloid- and lymphoid-like cells. This model presents an easy-to-use, high-throughput, reproducible and scalable platform to probe multifaceted aspects of human development and blood formation at the early post-implantation stage. It will provide a tractable human-based model for drug testing and disease modelling.

Adapting to change: insights from new organisms in cell and developmental biology.

We are living in an era of environmental change with undeniable parallels with past mass extinctions. To improve our understanding of planetary health and resilience, we must expand our research beyond traditional lab models. Forecasting the future of biological diversity relies on extrapolation of past trends, which necessitates the study of a wider range of biological systems. The 'Unconventional and Emerging Experimental Organisms for Cell and Developmental Biology' meeting, which took place in Dorking, UK, in September 2023, emphasized the importance of this broader approach. Discussions centered on evolutionary innovation, robustness and diversity, underscoring the need for broader taxon sampling and novel experimental models to address current and future challenges.

Historic obstacles and emerging opportunities in the field of developmental metabolism - lessons from Heidelberg.

The field of developmental metabolism is experiencing a technological revolution that is opening entirely new fields of inquiry. Advances in metabolomics, small-molecule sensors, single-cell RNA sequencing and computational modeling present new opportunities for exploring cell-specific and tissue-specific metabolic networks, interorgan metabolic communication, and gene-by-metabolite interactions in time and space. Together, these advances not only present a means by which developmental biologists can tackle questions that have challenged the field for centuries, but also present young scientists with opportunities to define new areas of inquiry. These emerging frontiers of developmental metabolism were at the center of a highly interactive 2023 EMBO workshop 'Developmental metabolism: flows of energy, matter, and information'. Here, we summarize key discussions from this forum, emphasizing modern developmental biology's challenges and opportunities.

Pathway to independence: perspectives on the future.

In this Perspective, our 2024 Pathway to Independence Fellows provide their thoughts on the future of their field. Covering topics as diverse as plant development, tissue engineering and adaptation to climate change, and using a wide range of experimental organisms, these talented postdocs showcase some of the major open questions and key challenges across the spectrum of developmental biology research.

Human developmental biology - a global perspective.

In the companion Perspective 'Past and future of human developmental biology' (Hopwood, 2024), historian Nick Hopwood proposes that the field of human developmental biology has gone through periods of attention and neglect. Development invited researchers from the field to respond to this idea. In this article, published to coincide with the 10th anniversary of Development's 'From Stem Cells to Human Development' meeting, researchers from eight countries comment on how they believe their local legal, political, regulatory, societal and technological frameworks are influencing the field's trajectory.

Past and future of human developmental biology.

Research directly on human embryos has gone through cycles of interest and neglect. The recent revitalization, including the making of 'human developmental biology', depended on fresh supplies of material and demand for medically relevant work. Human studies relied on mice but rejected simple extrapolation from this model mammal. Now, it is time to take stock while scanning the horizon for further change. Will research on human development be facilitated or frustrated? Will comparative approaches bring a greater variety of animal models into the picture? Will human stem-cell-based embryo models secure ever larger roles as exemplars of vertebrate development?

Generative models of morphogenesis in developmental biology.

Understanding the mechanism by which cells coordinate their differentiation and migration is critical to our understanding of many fundamental processes such as wound healing, disease progression, and developmental biology. Mathematical models have been an essential tool for testing and developing our understanding, such as models of cells as soft spherical particles, reaction-diffusion systems that couple cell movement to environmental factors, and multi-scale multi-physics simulations that combine bottom-up rule-based models with continuum laws. However, mathematical models can often be loosely related to data or have so many parameters that model behaviour is weakly constrained. Recent methods in machine learning introduce new means by which models can be derived and deployed. In this review, we discuss examples of mathematical models of aspects of developmental biology, such as cell migration, and how these models can be combined with these recent machine learning methods.

The people behind the papers - Qiongxuan Lu, Yuan Gao and Bo Dong.

In many animal embryos, the tail bends ventrally as it grows, but the underlying mechanisms driving this multi-tissue deformation have been difficult to study. A new paper in Development uses the simple chordate Ciona as a model to study this widely conserved process. To find out more about the story, we met the paper's two first authors, Qiongxuan Lu and Yuan Gao, and their supervisor Bo Dong, Professor at the Ocean University of China in Qingdao, China.

The people behind the papers - Chase Bryan and Kristen Kwan.

Optic cup development involves a series of intricate cell and tissue movements, and cells' interaction with the extracellular matrix (ECM) is known to play an important role. However, the details of how ECM components work in eye development, and where they come from, is still poorly understood, and is the subject of a new Development paper that takes advantage of live imaging in zebrafish embryos. We caught up with first author Chase Bryan and his supervisor Kristen Kwan, Assistant Professor in the Department of Human Genetics at the University of Utah, Salt Lake City, to find out more about the story.

On growth and force: mechanical forces in development.

The EMBO/EMBL Symposium 'Mechanical Forces in Development' was held in Heidelberg, Germany, on 3-6 July 2019. This interdisciplinary symposium brought together an impressive and diverse line-up of speakers seeking to address the origin and role of mechanical forces in development. Emphasising the importance of integrative approaches and theoretical simulations to obtain comprehensive mechanistic insights into complex morphogenetic processes, the meeting provided an ideal platform to discuss the concepts and methods of developmental mechanobiology in an era of fast technical and conceptual progress. Here, we summarise the concepts and findings discussed during the meeting, as well as the agenda it sets for the future of developmental mechanobiology.

Evolution of organoid technology: Lessons learnt in Co-Culture systems from developmental biology.

In recent years, the development of 3D organoids has opened new avenues of investigation into development, physiology, and regenerative medicine. Organoid formation and the process of organogenesis share common developmental pathways; thus, our knowledge of developmental biology can help model the complexity of different organs to refine organoids into a more sophisticated platform. The developmental process is strongly dependent on complex networks and communication of cell-cell and cell-matrix interactions among different cell populations and their microenvironment, during embryogenesis. These interactions affect cell behaviors such as proliferation, survival, migration, and differentiation. Co-culture systems within the organoid technology were recently developed and provided the highly physiologically relevant systems. Supportive cells including various types of endothelial and stromal cells provide the proper microenvironment, facilitate organoid assembly, and improve vascularization and maturation of organoids. This review discusses the role of the co-culture systems in organoid generation, with a focus on how knowledge of developmental biology has directed and continues to shape the development of more evolved 3D co-culture system-derived organoids.

An interview with Bénédicte Sanson.

Bénédicte Sanson is a Reader in Developmental Morphogenesis and Wellcome Trust Investigator at the Department of Physiology, Development and Neuroscience at the University of Cambridge. Her lab works on axis extension and compartmental boundary formation in the Drosophila embryo, combining genetics with quantitative and computational approaches. In 2019 she was awarded the British Society for Developmental Biology's Cheryll Tickle medal, which recognises outstanding achievements in developmental biology of mid-career female researchers. We caught up with Bénédicte in a café close to her lab and discussed how she started research not with flies but with phages and how collaboration and interdisciplinarity have always been at the core of her science.

Human in vitro fertilisation and developmental biology: a mutually influential history.

This article describes the origins and development of in vitro fertilisation (IVF) and how it was influenced by, and influenced, basic research in developmental biology. It describes the technical and social challenges that confronted the pioneers in this field of study, and the considerable progress that has been made since those early days. It also considers how IVF has contributed, and continues to contribute, to our understanding of early human development.

The people behind the papers - Daniel Osório, Elaine Chan, Joana Saramago and Ana Carvalho.

Animal cytokinesis is driven by an actomyosin ring that assembles at the cell equator and constricts to physically separate the two daughters. Although myosin is known to be essential for cytokinesis in multiple systems, whether this requirement reflects its motor or actin crosslinking activities has recently been a matter of contention. A new paper in Development now addresses this problem using the first divisions of the Caenorhabditis elegans embryo as a model. We caught up with the paper's three first authors Daniel Osório, Elaine Chan and Joana Saramago, and their supervisor Ana Carvalho, Principal Investigator at the University of Porto's i3S consortium, to find out more about the story.

The people behind the papers - Amsha Proag and Magali Suzanne.

During development, mechanical forces sculpt tissues into myriad forms. Actomyosin contractility generated within the cell has an increasingly appreciated role in this process, but how tissue forces relate to the physical properties of the extracellular matrix is still poorly understood, particularly at longer time scales and the whole tissue level. A new paper in Development addresses these issues using Drosophila leg development as a model, taking advantage of an ex vivo culturing method. We caught up with first author Amsha Proag and last author Magali Suzanne, group leader at the Centre for Integrative Biology in Toulouse, France, to hear more about the story.

The people behind the papers - Eduardo Leyva-Díaz and Oliver Hobert.

Transcriptional autoregulation occurs when transcription factors bind their own cis-regulatory sequences, ensuring their own continuous expression along with expression of other targets. During development, continued expression of identity-specifying transcription factors can be achieved by autoregulation, but until now formal evidence for a developmental requirement of autoregulation has been lacking. A new paper in Development provides this proof with the help of CRISPR/Cas9 gene editing in the C. elegans nervous system. We caught up with the paper's two authors: postdoc Eduardo Leyva-Díaz and his supervisor Oliver Hobert, Professor of Biological Sciences and HHMI Investigator at Columbia University, New York, to find out more about the work.

A periodic table of cell types.

Single cell biology is currently revolutionizing developmental and evolutionary biology, revealing new cell types and states in an impressive range of biological systems. With the accumulation of data, however, the field is grappling with a central unanswered question: what exactly is a cell type? This question is further complicated by the inherently dynamic nature of developmental processes. In this Hypothesis article, we propose that a 'periodic table of cell types' can be used as a framework for distinguishing cell types from cell states, in which the periods and groups correspond to developmental trajectories and stages along differentiation, respectively. The different states of the same cell type are further analogous to 'isotopes'. We also highlight how the concept of a periodic table of cell types could be useful for predicting new cell types and states, and for recognizing relationships between cell types throughout development and evolution.

Recording development with single cell dynamic lineage tracing.

Every animal grows from a single fertilized egg into an intricate network of cell types and organ systems. This process is captured in a lineage tree: a diagram of every cell's ancestry back to the founding zygote. Biologists have long sought to trace this cell lineage tree in individual organisms and have developed a variety of technologies to map the progeny of specific cells. However, there are billions to trillions of cells in complex organisms, and conventional approaches can only map a limited number of clonal populations per experiment. A new generation of tools that use molecular recording methods integrated with single cell profiling technologies may provide a solution. Here, we summarize recent breakthroughs in these technologies, outline experimental and computational challenges, and discuss biological questions that can be addressed using single cell dynamic lineage tracing.