Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.

Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and 2R occurred in the gnathostome stem-lineage, maximally in the late Cambrian–earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced an additional independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only in the gnathostome but not in the cyclostome lineage, calling into question the general expectation that WGDs lead to leaps of bodyplan complexity.

Background: Mesenchymal Stem/Stromal Cells (MSCs) define a population of progenitor cells capable of giving rises to at least three mesodermal lineages in vitro, the chondrocytes, osteoblasts and adipocytes. The validity of MSCs in vivo has been questioned because their existence, either as a homogeneous progenitor cell population or as a stem cell lineage, has been difficult to prove. The wide use of primary MSCs in regenerative and therapeutic applications raises ethical and regulatory concerns in many countries. In contrast to hematopoietic stem cells, a parallel concept which carries an embryological emphasis from its outset, MSCs have attracted little interest among developmental biologists and the embryological basis for their existence, or lack thereof, has not been carefully evaluated. Methods: This article provides a brief, embryological overview of these three mesoderm cell lineages and offers a framework of ontological rationales for the potential existence of MSCs in vivo. Results: Emphasis is given to the common somatic lateral plate mesoderm origin of the majority of body’s adipose and skeletal tissues and of the major sources used for MSC derivation clinically. Support for the MSC hypothesis also comes from a large body of molecular and lineage analysis data in vivo. Conclusions: It is concluded that despite the lack of a definitive proof, the MSC concept has a firm embryological basis and that advances in MSC research can be facilitated by achieving a better integration with developmental biology.

Cap Analysis of Gene Expression (CAGE) in combination with single-molecule sequencing technology allows precision mapping of transcription start sites (TSSs) and genome-wide capture of promoter activities in differentiated and steady state cell populations. Much less is known about whether TSS profiling can characterize diverse and non-steady state cell populations, such as the approximately 400 transitory and heterogeneous cell types that arise during ontogeny of vertebrate animals. To gain such insight, we used the chick model and performed CAGE-based TSS analysis on embryonic samples covering the full 3-week developmental period. In total, 31,863 robust TSS peaks (>1 tag per million [TPM]) were mapped to the latest chicken genome assembly, of which 34% to 46% were active in any given developmental stage. ZENBU, a web-based, open-source platform, was used for interactive data exploration. TSSs of genes critical for lineage differentiation could be precisely mapped and their activities tracked throughout development, suggesting that non-steady state and heterogeneous cell populations are amenable to CAGE-based transcriptional analysis. Our study also uncovered a large set of extremely stable housekeeping TSSs and many novel stage-specific ones. We furthermore demonstrated that TSS mapping could expedite motif-based promoter analysis for regulatory modules associated with stage-specific and housekeeping genes. Finally, using Brachyury as an example, we provide evidence that precise TSS mapping in combination with Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-on technology enables us, for the first time, to efficiently target endogenous avian genes for transcriptional activation. Taken together, our results represent the first report of genome-wide TSS mapping in birds and the first systematic developmental TSS analysis in any amniote species (birds and mammals). By facilitating promoter-based molecular analysis and genetic manipulation, our work also underscores the value of avian models in unravelling the complex regulatory mechanism of cell lineage specification during amniote development. Early development cannot be studied in humans. Analysis of embryogenesis using avian models, which are phylogenetically closely related to mammals, can help us understand the complex regulatory mechanism of cell lineage specification during human development. We monitored the 3 weeks of chicken embryonic development from newly-laid egg to the point of hatching via CAGE expression profiling and revealed the first avian genome-wide set of genuine transcription start sites (TSSs) critical for differentiation and maturation from pregastrulation to hatching. By analyzing stage-specific expression profiles, we have identified enriched transcription factors responsible for lineage commitment and their corresponding regulatory modules. In addition, we reported a set of stable housekeeping genes more suitable for cross-sample normalization and calibration. Finally, we demonstrated the utility of a CAGE-based TSS dataset in developmental studies. Using the Brachyury gene as an example, we showed that CRISPR/Cas9-based genome-editing tools can be efficiently employed to target and transcriptionally activate the promoters of virtually any endogenous genes, enabled by the knowledge of their precise TSS locations. Our data, made available for easy exploration through the open ZENBU platform, represent an invaluable resource to study early development in amniotes.

The nonconserved primitive streak: In human development, a linear structure called the primitive streak appears 14 days after fertilization. This structure marks the transition of the embryo from having radial to bilateral symmetry. The primitive streak also gives anterior-posterior and dorsal-ventral spatial information to cells undergoing gastrulation and forming the various body cell types. In a Review, Sheng et al . present a phylogenetic and ontogenetic overview of the primitive streak. They discuss organismal, cellular, and molecular features of the primitive streak and how it functions in amniote gastrulation. The observation that this structure is not conserved and is not required for development in vitro has implications for embryonic stem cell–based models and considerations about human development research. —BAP

Isthmin1 (ISM1) was originally identified as a fibroblast group factor expressed in Xenopus laevis embryonic brain, but its biological functions remain unclear. The spatiotemporal distribution of ISM1, with high expression in the anterior primitive streak of the chick embryo and the anterior mesendoderm of the mouse embryo, suggested that ISM1 may regulate signaling by the NODAL subfamily of TGB-β cytokines that control embryo patterning. We report that ISM1 is an inhibitor of NODAL signaling. ISM1 has little effect on TGF-β1, ACTIVIN-A, or BMP4 signaling but specifically inhibits NODAL-induced phosphorylation of SMAD2. In line with this observation, ectopic ISM1 causes defective left-right asymmetry and abnormal heart positioning in chick embryos. Mechanistically, ISM1 interacts with NODAL ligand and type I receptor ACVR1B through its AMOP domain, which compromises the NODAL–ACVR1B interaction and down-regulates phosphorylation of SMAD2. Therefore, we identify ISM1 as an extracellular antagonist of NODAL and reveal a negative regulatory mechanism that provides greater plasticity for the fine-tuning of NODAL signaling.