Whole-Mount Histochemical Protocols in Zebrafish for a Hands-On Developmental Biology Practical Course in Ecuador.

Research-based education at the undergraduate level is ideal for fostering the training of future scientists. In an undergraduate Developmental Biology course, this learning strategy requires the availability of model species and enough research reagents, not only for technique training but also for the development of student original projects. This might be challenging in most countries, where resources are limited. Hence, there is a need to develop low-cost solutions for use in the classroom. In this study, we describe the optimization and use of two low-cost protocols in zebrafish embryos for hands-on practical sessions and project-based learning in a Developmental Biology undergraduate course in Ecuador. These protocols were designed for the practical and experimental learning of vertebrate meroblastic cleavage, gastrulation, and neural crest differentiation. The proposed protocols have been previously described in the literature and use silver nitrate and alcian blue, two relatively inexpensive reagents, to label cell membranes and cartilage. The silver nitrate protocol allows the study of cell contact formation during cleavage and the identification of cellular changes during gastrulation, including yolk internalization and epiboly. The alcian blue staining allows the analysis of cranial mesenchymal differentiation into cartilage. These protocols are ideal for practical sessions due to their ease of application, quick results, adaptability to the class schedule, and robustness in the hands of beginning researchers. Finally, these protocols are adaptable for research-based class projects.

The organizer: What it meant, and still means, to developmental biology.

This article is about how the famous organizer experiment has been perceived since it was first published in 1924. The experiment involves the production of a secondary embryo under the influence of a graft of a dorsal lip from an amphibian gastrula to a host embryo. The early experiments of Spemann and his school gave rise to a view that the whole early amphibian embryo was "indifferent" in terms of determination, except for a special region called "the organizer". This was viewed mainly as an agent of neural induction, also having the ability to generate an anteroposterior body pattern. Early biochemical efforts to isolate a factor emitted by the organizer were not successful but culminated in the definition of "neuralizing (N)" and "mesodermalizing (M)" factors present in a wide variety of animal tissues. By the 1950s this view became crystallized as a "two gradient" model involving the N and M factors, which explained the anteroposterior patterning effect. In the 1970s, the phenomenon of mesoderm induction was characterized as a process occurring before the commencement of gastrulation. Reinvestigation of the organizer effect using lineage labels gave rise to a more precise definition of the sequence of events. Since the 1980s, modern research using the tools of molecular biology, combined with microsurgery, has explained most of the processes involved. The organizer graft should now be seen as an experiment which involves multiple interactions: dorsoventral polarization following fertilization, mesoderm induction, the dorsalizing signal responsible for neuralization and dorsoventral patterning of the mesoderm, and additional factors responsible for anteroposterior patterning.

Utilizing developmental dynamics for evolutionary prediction and control.

Understanding, predicting, and controlling the phenotypic consequences of genetic and environmental change is essential to many areas of fundamental and applied biology. In evolutionary biology, the generative process of development is a major source of organismal evolvability that constrains or facilitates adaptive change by shaping the distribution of phenotypic variation that selection can act upon. While the complex interactions between genetic and environmental factors during development may appear to make it impossible to infer the consequences of perturbations, the persistent observation that many perturbations result in similar phenotypes indicates that there is a logic to what variation is generated. Here, we show that a general representation of development as a dynamical system can reveal this logic. We build a framework that allows predicting the phenotypic effects of perturbations, and conditions for when the effects of perturbations of different origins are concordant. We find that this concordance is explained by two generic features of development, namely the dynamical dependence of the phenotype on itself and the fact that all perturbations must affect the developmental process to have an effect on the phenotype. We apply our theoretical framework to classical models of development and show that it can be used to predict the evolutionary response to selection using information of plasticity and to accelerate evolution in a desired direction. The framework we introduce provides a way to quantitatively interchange perturbations, opening an avenue of perturbation design to control the generation of variation.

Role and ethics of cynomolgus monkey (Macaca fascicularis) blastoids in primate developmental biology research.

This review on cynomolgus monkey (Macaca fascicularis) blastoids discusses a breakthrough in modeling early non-human primate embryogenesis, offering insights into embryonic development and implantation processes. It acknowledges ethical challenges and animal welfare considerations in developmental biology, suggests potential applications in human reproductive medicine, and highlights the need for ongoing ethical and technical refinement.

Onco-Breastomics: An Eco-Evo-Devo Holistic Approach.

Known as a diverse collection of neoplastic diseases, breast cancer (BC) can be hyperbolically characterized as a dynamic pseudo-organ, a living organism able to build a complex, open, hierarchically organized, self-sustainable, and self-renewable tumor system, a population, a species, a local community, a biocenosis, or an evolving dynamical ecosystem (i.e., immune or metabolic ecosystem) that emphasizes both developmental continuity and spatio-temporal change. Moreover, a cancer cell community, also known as an oncobiota, has been described as non-sexually reproducing species, as well as a migratory or invasive species that expresses intelligent behavior, or an endangered or parasite species that fights to survive, to optimize its features inside the host's ecosystem, or that is able to exploit or to disrupt its host circadian cycle for improving the own proliferation and spreading. BC tumorigenesis has also been compared with the early embryo and placenta development that may suggest new strategies for research and therapy. Furthermore, BC has also been characterized as an environmental disease or as an ecological disorder. Many mechanisms of cancer progression have been explained by principles of ecology, developmental biology, and evolutionary paradigms. Many authors have discussed ecological, developmental, and evolutionary strategies for more successful anti-cancer therapies, or for understanding the ecological, developmental, and evolutionary bases of BC exploitable vulnerabilities. Herein, we used the integrated framework of three well known ecological theories: the Bronfenbrenner's theory of human development, the Vannote's River Continuum Concept (RCC), and the Ecological Evolutionary Developmental Biology (Eco-Evo-Devo) theory, to explain and understand several eco-evo-devo-based principles that govern BC progression. Multi-omics fields, taken together as onco-breastomics, offer better opportunities to integrate, analyze, and interpret large amounts of complex heterogeneous data, such as various and big-omics data obtained by multiple investigative modalities, for understanding the eco-evo-devo-based principles that drive BC progression and treatment. These integrative eco-evo-devo theories can help clinicians better diagnose and treat BC, for example, by using non-invasive biomarkers in liquid-biopsies that have emerged from integrated omics-based data that accurately reflect the biomolecular landscape of the primary tumor in order to avoid mutilating preventive surgery, like bilateral mastectomy. From the perspective of preventive, personalized, and participatory medicine, these hypotheses may help patients to think about this disease as a process governed by natural rules, to understand the possible causes of the disease, and to gain control on their own health.

Pluripotency of a founding field: rebranding developmental biology.

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional funding apparatuses, frameworks for interdisciplinary innovative collaborations, pedagogical access, improved science communication, increased diversity and inclusion, and equity of resources to provide maximal impact to the community.

Harmony in chaos: understanding cancer through the lenses of developmental biology.

When we think about cancer, the link to development might not immediately spring to mind. Yet, many foundational concepts in cancer biology trace their roots back to developmental processes. Several defining traits of cancer were indeed initially observed and studied within developing embryos. As our comprehension of embryonic mechanisms deepens, it not only illuminates how and why cancer cells hijack these processes but also spearheads the emergence of innovative technologies for modeling and comprehending tumor biology. Among these technologies are stem cell-based models, made feasible through our grasp of fundamental mechanisms related to embryonic development. The intersection between cancer and stem cell research is evolving into a tangible synergy that extends beyond the concepts of cancer stem cells and cell-of-origin, offering novel tools to unravel the mechanisms of cancer initiation and progression.

The expanding footprint of basic biology research in India.

Basic biology research in India has expanded in recent years, and addressing key challenges should enable this momentum to continue.

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.

Unravelling the sexual developmental biology of Cystoisospora suis, a model for comparative coccidian parasite studies.

Introduction: The apicomplexan parasite Cystoisospora suis has global significance as an enteropathogen of suckling piglets. Its intricate life cycle entails a transition from an asexual phase to sexual development, ultimately leading to the formation of transmissible oocysts. Methods: To advance our understanding of the parasite's cellular development, we complemented previous transcriptome studies by delving into the proteome profiles at five distinct time points of in vitro cultivation through LC/MS-MS analysis. Results: A total of 1,324 proteins were identified in the in vitro developmental stages of C. suis, and 1,082 proteins were identified as significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD045050. We performed BLAST, GO enrichment, and KEGG pathway analyses on the up- and downregulated proteins to elucidate correlated events in the C. suis life cycle. Our analyses revealed intriguing metabolic patterns in macromolecule metabolism, DNA- and RNA-related processes, proteins associated with sexual stages, and those involved in cell invasion, reflecting the adaptation of sexual stages to a nutrient-poor and potentially stressful extracellular environment, with a focus on enzymes involved in metabolism and energy production. Discussion: These findings have important implications for understanding the developmental biology of C. suis as well as other, related coccidian parasites, such as Eimeria spp. and Toxoplasma gondii. They also support the role of C. suis as a new model for the comparative biology of coccidian tissue cyst stages.

An interview with Jonathan Slack.

Jonathan Slack is Emeritus Professor at the University of Bath. His research interests have included early development of the Xenopus embryo, regeneration of limbs and tails, and attempts to reprogramme other cell types to ß cells. In September 2023, Jonathan was awarded the 2023 British Society for Developmental Biology Wolpert Medal, which recognizes an outstanding individual who has made major contributions to the teaching and communication of developmental biology in the UK. We chatted to Jonathan at the European Developmental Biology Congress, where he was presented with the medal, to find out more about his career and his experience writing textbooks and the 'A Very Short Introduction' books on stem cells and genes.

An interview with Marysia Placzek.

Marysia Placzek is Professor of Developmental Neurobiology at the University of Sheffield, UK, where her lab studies the development of the hypothalamus. In 2023, she was awarded the British Society for Developmental Biology's (BSDB) Waddington Medal, which recognises outstanding individuals who have made major contributions to UK developmental biology. Marysia gave her award lecture at the European Developmental Biology Congress (EDBC), a hybrid meeting with hubs in Oxford, Paris and Barcelona. We met in Oxford after her talk to learn more about her research, her love of teaching and her thoughts on the future of the field.

An interview with Aimee Jaramillo-Lambert.

Aimee Jaramillo-Lambert is currently an Assistant Professor at the University of Delaware. Aimee was awarded the Society for Developmental Biology 2023 Elizabeth D. Hay New Investigator Award in recognition of her outstanding research in developmental biology during the early stages of her independent career. We caught up with Aimee over a video call to talk about her research into sexual reproduction in Caenorhabditis elegans, the importance of mentorship, and what drives her work in diversity, equity and inclusion.

A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond.

Recent discoveries in stem cell and developmental biology have introduced a new era marked by the generation of in vitro models that recapitulate early mammalian development, providing unprecedented opportunities for extensive research in embryogenesis. Here, we present an overview of current techniques that model early mammalian embryogenesis, specifically noting models created from stem cells derived from two significant species: Homo sapiens, for its high relevance, and Mus musculus, a historically common and technically advanced model organism. We aim to provide a holistic understanding of these in vitro models by tracing the historical background of the progress made in stem cell biology and discussing the fundamental underlying principles. At each developmental stage, we present corresponding in vitro models that recapitulate the in vivo embryo and further discuss how these models may be used to model diseases. Through a discussion of these models as well as their potential applications and future challenges, we hope to demonstrate how these innovative advances in stem cell research may be further developed to actualize a model to be used in clinical practice.

Developmental biology: A hole in the matrix.

Neurons must access the environment to gather information, but this exposure must be carefully managed. New work finds that glial cells, the non-neuronal component of the nervous system, control environmental access by stage- and sex-specific patterning of the extracellular matrix.

Pathway to Independence: the future of developmental biology.

In 2022, Development launched its Pathway to Independence (PI) Programme, aimed at supporting postdocs as they transition to their first independent position. We selected eight talented researchers as the first cohort of PI Fellows. In this article, each of our Fellows provides their perspective on the future of their field. Together, they paint an exciting picture of the current state of and open questions in developmental biology.

Craniofacial developmental biology in the single-cell era.

The evolution of a unique craniofacial complex in vertebrates made possible new ways of breathing, eating, communicating and sensing the environment. The head and face develop through interactions of all three germ layers, the endoderm, ectoderm and mesoderm, as well as the so-called fourth germ layer, the cranial neural crest. Over a century of experimental embryology and genetics have revealed an incredible diversity of cell types derived from each germ layer, signaling pathways and genes that coordinate craniofacial development, and how changes to these underlie human disease and vertebrate evolution. Yet for many diseases and congenital anomalies, we have an incomplete picture of the causative genomic changes, in particular how alterations to the non-coding genome might affect craniofacial gene expression. Emerging genomics and single-cell technologies provide an opportunity to obtain a more holistic view of the genes and gene regulatory elements orchestrating craniofacial development across vertebrates. These single-cell studies generate novel hypotheses that can be experimentally validated in vivo. In this Review, we highlight recent advances in single-cell studies of diverse craniofacial structures, as well as potential pitfalls and the need for extensive in vivo validation. We discuss how these studies inform the developmental sources and regulation of head structures, bringing new insights into the etiology of structural birth anomalies that affect the vertebrate head.

Integrating Complex Life Cycles in Comparative Developmental Biology.

The goal of comparative developmental biology is identifying mechanistic differences in embryonic development between different taxa and how these evolutionary changes have led to morphological and organizational differences in adult body plans. Much of this work has focused on direct-developing species in which the adult forms straight from the embryo and embryonic modifications have direct effects on the adult. However, most animal lineages are defined by indirect development, in which the embryo gives rise to a larval body plan and the adult forms by transformation of the larva. Historically, much of our understanding of complex life cycles is viewed through the lenses of ecology and zoology. In this review, we discuss the importance of establishing developmental rather than morphological or ecological criteria for defining developmental mode and explicitly considering the evolutionary implications of incorporating complex life cycles into broad developmental comparisons of embryos across metazoans.