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?

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.

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.

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 term "caline" in plant developmental biology.

In the 1930s, Frits Warmolt Went conducted a number of seminal studies on pea seedlings that had been germinated in the dark and assessed their growth when either the apical parts, cotyledons, or roots were cut off or grafted, to assess whether coplant growth factors assisted auxin in the development of these organs. Went assigned the term "calines" to all auxin-assisting substances, specifically rhizocaline, caulocaline, and phyllocaline in root, shoot (and axillary buds) and leaf development, respectively. Those experiments were based exclusively on growth assays, and no supplementary biochemical or physiological analyses were ever conducted, and additional proof was only provided by Went using pea or tomato. The lack of independent reproducibility by other groups, combined with the fact that the hormonal control of these developmental events in plants is now fairly well-studied event, even at the molecular level, suggests that these growth factors that Went observed 80 years ago either do not exist or are known by some other term in modern plant development. The terms related to "calines" should thus no longer be used in plant developmental biology.

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.

Non-model systems in mammalian forelimb evo-devo.

Mammal forelimbs are highly diverse, ranging from the elongated wing of a bat to the stout limb of the mole. The mammal forelimb has been a long-standing system for the study of early developmental patterning, proportional variation, shape change, and the reduction of elements. However, most of this work has been performed in mice, which neglects the wide variation present across mammal forelimbs. This review emphasizes the critical role of non-model systems in limb evo-devo and highlights new emerging models and their potential. We discuss the role of gene networks in limb evolution, and touch on functional analyses that lay the groundwork for further developmental studies. Mammal limb evo-devo is a rich field, and here we aim to synthesize the findings of key recent works and the questions to which they lead.

From Aedes to Zeugodacus: a review of dipteran body coloration studies regarding evolutionary developmental biology, pest control, and species discovery.

Over the past two decades, evo-devo (evolution of development) studies have elucidated genetic mechanisms underlying novel dipteran body color patterns. Here we review the most recent developments, which show some departure from the model organism Drosophila melanogaster, leading the field into the investigation of more complex color patterns. We also discuss how the robust application of transgenic techniques has facilitated the study of many non-model pest species. Furthermore, we see that subtle pigmentation differences guide the discovery and description of new dipterans. Therefore, we argue that the existence of new field guides and the prevalence of pigmentation studies in non-model flies will enable scientists to adopt uninvestigated species into the lab, allowing them to study novel morphologies.

Changes in Cardiomyocyte Cell Cycle and Hypertrophic Growth During Fetal to Adult in Mammals.

The failure of adult cardiomyocytes to reproduce themselves to repair an injury results in the development of severe cardiac disability leading to death in many cases. The quest for an understanding of the inability of cardiac myocytes to repair an injury has been ongoing for decades with the identification of various factors which have a temporary effect on cell-cycle activity. Fetal cardiac myocytes are continuously replicating until the time that the developing fetus reaches a stage of maturity sufficient for postnatal life around the time of birth. Recent reports of the ability for early neonatal mice and pigs to completely repair after the severe injury has stimulated further study of the regulators of the cardiomyocyte cell cycle to promote replication for the remuscularization of injured heart. In all mammals just before or after birth, single-nucleated hyperplastically growing cardiomyocytes, 1X2N, undergo ≥1 additional DNA replications not followed by cytokinesis, resulting in cells with ≥2 nuclei or as in primates, multiple DNA replications (polyploidy) of 1 nucleus, 2X2(+)N or 1X4(+)N. All further growth of the heart is attributable to hypertrophy of cardiomyocytes. Animal studies ranging from zebrafish with 100% 1X2N cells in the adult to some strains of mice with up to 98% 2X2N cells in the adult and other species with variable ratios of 1X2N and 2X2N cells are reviewed relative to the time of conversion. Various structural, physiologic, metabolic, genetic, hormonal, oxygenation, and other factors that play a key role in the inability of post-neonatal and adult myocytes to undergo additional cytokinesis are also reviewed.

Virtual meeting, real and sound science: report of the 17th Meeting of the Spanish Society for Developmental Biology (SEBD-2020).

The Spanish Society for Developmental Biology (SEBD) organized its 17th meeting in November 2020 (herein referred to as SEBD2020). This meeting, originally programmed to take place in the city of Bilbao, was forced onto an online format due to the SARS-CoV2, COVID-19 pandemic. Although, we missed the live personal interactions and missed out on the Bilbao social scene, we were able to meet online to present our work and discuss our latest results. An overview of the activities that took place around the meeting, the different scientific sessions and the speakers involved are presented here. The pros and cons of virtual meetings are discussed.

Early and late stages of Developmental Biology in Argentina.

The history of science in Argentina is based on the enormous contribution that the great immigration of the 19th and 20th centuries produced in the country. The scientific and philosophical ideas and the role played especially by Italian scientists who arrived in the country produced a great impact on the different disciplines including Development Biology in emerging universities. The University of Tucumán pioneered the study of experimental biology, making important contributions to reproductive biology and to the early development of amphibians. The contribution of the Italian embryologist Armando Pisanó and the Argentinian Francisco D. Barbieri expanded the field to other universities and research centers located in Córdoba, La Plata, Bahía Blanca and Rosario. Given its strategic position, laboratories located in the city of Buenos Aires reached technological advances faster than others. Indeed, these laboratories saw the evolution from experimental biology to developmental genetics, renewing interest in this area. Currently, Developmental Biology brings together young researchers eager to consolidate regional and global collaboration networks that seek to help solve specific problems such as fertility, epigenetics, stem cells and tissue engineering.