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The "ribbon," a structural arrangement in which Golgi stacks connect to each other, is considered to be restricted to vertebrate cells. Although ribbon disruption is linked to various human pathologies, its functional role in cellular processes remains unclear. In this study, we investigate the evolutionary origin of the Golgi ribbon. We observe a ribbon-like architecture in the cells of several metazoan taxa suggesting its early emergence in animal evolution predating the appearance of vertebrates. Supported by AlphaFold2 modeling, we propose that the evolution of Golgi reassembly and stacking protein (GRASP) binding by golgin tethers may have driven the joining of Golgi stacks resulting in the ribbon-like configuration. Additionally, we find that Golgi ribbon assembly is a shared developmental feature of deuterostomes, implying a role in embryogenesis. Overall, our study points to the functional significance of the Golgi ribbon beyond vertebrates and underscores the need for further investigations to unravel its elusive biological roles., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The assembly of the neuronal and other major cell type programs occurred early in animal evolution. We can reconstruct this process by studying non-bilaterians like placozoans. These small disc-shaped animals not only have nine morphologically described cell types and no neurons but also show coordinated behaviors triggered by peptide-secreting cells. We investigated possible neuronal affinities of these peptidergic cells using phylogenetics, chromatin profiling, and comparative single-cell genomics in four placozoans. We found conserved cell type expression programs across placozoans, including populations of transdifferentiating and cycling cells, suggestive of active cell type homeostasis. We also uncovered fourteen peptidergic cell types expressing neuronal-associated components like the pre-synaptic scaffold that derive from progenitor cells with neurogenesis signatures. In contrast, earlier-branching animals like sponges and ctenophores lacked this conserved expression. Our findings indicate that key neuronal developmental and effector gene modules evolved before the advent of cnidarian/bilaterian neurons in the context of paracrine cell signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The innovation of multicellularity has driven the unparalleled evolution of animals (Metazoa). But how is a multicellular organism formed and how is its architecture maintained faithfully? The defining properties and rules required for the establishment of the architecture of multicellular organisms include the development of adhesive cell interactions, orientation of division axis, and the ability to reposition daughter cells over long distances. Central to all these properties is the ability to generate asymmetry (polarity), coordinated by a highly conserved set of proteins known as cell polarity regulators. The cell polarity complexes, Scribble, Par and Crumbs, are considered to be a metazoan innovation with apicobasal polarity and adherens junctions both believed to be present in all animals. A better understanding of the fundamental mechanisms regulating cell polarity and tissue architecture should provide key insights into the development and regeneration of all animals including humans. Here we review what is currently known about cell polarity and its control in the most basal metazoans, and how these first examples of multicellular life can inform us about the core mechanisms of tissue organisation and repair, and ultimately diseases of tissue organisation, such as cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wright, Kvansakul, Schierwater and Humbert.)

For over 20 years, the Schmid Training Course (STC) has offered unique opportunities for marine biology students from European universities to learn about marine model organisms. While the topics of the course have continuously changed over the years with the advent of new research techniques and discoveries, the pedagogical approach has remained largely the same - a combination of lectures, lab practicals, and field excursions. Several life science researchers, who have taught in the STC for many years, sought to bring the course's pedagogical approach into the 21st century, and with the support of Erasmus+ Programme of the European Community funding, the Digital Marine project was developed. Digital Marine began in 2018 as an international partnership between the six research centers from which the STC instructors hail, and its main objective was to introduce a flipped, blended approach to learning and teaching with respect to established and emerging marine biological model systems. The Digital Marine platform, which covers 12 marine model organisms, is now publicly available., (© 2022 Wiley Periodicals LLC.)

Placozoans are a promising model system to study fundamental regeneration processes in a morphologically and genetically very simple animal. We here provide a brief introduction to the enigmatic Placozoa and summarize the state of the art of animal handling and experimental manipulation possibilities., (© 2022. The Author(s).)

Background: We previously reported on a pilot study to assess the incorporation of a novel wellness assessment device, the Preventiometer (iPEx5 GmbH, Greifswald, Germany), into an academic medical practice. The present follow-up study expands on those data and evaluates the acceptability of the assessment process in a larger sample population., Objective: The aim of this study was to evaluate participant satisfaction with the Preventiometer wellness assessment., Methods: A total of 60 healthy volunteers participated. Each participant underwent a comprehensive wellness assessment with the Preventiometer and received data from more than 30 diagnostic tests. A 32-question survey (with a numeric rating scale from 0 to 10) was used to rate the wellness assessment tests and participants' impressions of the wellness assessment., Results: Each assessment had a significantly higher rating than 7 ( P < .001), and the majority of participants agreed or strongly agreed that they were satisfied (98.3%), and they strongly agreed that they were engaged the entire time (93.2%), and liked the instant test results feature of the Preventiometer device (93.2%)., Conclusion: This study confirms findings from our previous pilot study regarding the feasibility of the Preventiometer as a wellness assessment tool. The study further demonstrated that 98% of participants were satisfied with the assessment and that all of them would recommend it to others., Competing Interests: Declaration of conflicting interests: Vilua Healthcare and the University Medicine Greifswald cooperate on a mobile health promotion project with the Preventiometer. Markus Krüger is employed at the University Medicine Greifswald with partial financial support from Vilua. The other authors declare that there are no conflicts of interest., (© The Author(s) 2021.)

The placozoan Trichoplax adhaerens has been bridging gaps between research disciplines like no other animal. As outlined in part 1, placozoans have been subject of hot evolutionary debates and placozoans have challenged some fundamental evolutionary concepts. Here in part 2 we discuss the exceptional genetics of the phylum Placozoa and point out some challenging model system applications for the best known species, Trichoplax adhaerens., (© 2021 The Authors. BioEssays published by Wiley Periodicals LLC.)

The placozoan Trichoplax adhaerens is a tiny hairy plate and more simply organized than any other living metazoan. After its original description by F.E. Schulze in 1883, it attracted attention as a potential model for the ancestral state of metazoan organization, the "Urmetazoon". Trichoplax lacks any kind of symmetry, organs, nerve cells, muscle cells, basal lamina, and extracellular matrix. Furthermore, the placozoan genome is the smallest (not secondarily reduced) genome of all metazoan genomes. It harbors a remarkably rich diversity of genes and has been considered the best living surrogate for a metazoan ancestor genome. The phylum Placozoa presently harbors three formally described species, while several dozen "cryptic" species are yet awaiting their description. The phylogenetic position of placozoans has recently become a contested arena for modern phylogenetic analyses and view-driven claims. Trichoplax offers unique prospects for understanding the minimal requirements of metazoan animal organization and their corresponding malfunctions., (© 2021 The Authors. BioEssays published by Wiley Periodicals LLC.)

There are considerable phylogenetic incongruencies between morphological and phylogenomic data for the deep evolution of animals. This has contributed to a heated debate over the earliest-branching lineage of the animal kingdom: the sister to all other Metazoa (SOM). Here, we use published phylogenomic data sets ($\sim $45,000-400,000 characters in size with $\sim $15-100 taxa) that focus on early metazoan phylogeny to evaluate the impact of incorporating morphological data sets ($\sim $15-275 characters). We additionally use small exemplar data sets to quantify how increased taxon sampling can help stabilize phylogenetic inferences. We apply a plethora of common methods, that is, likelihood models and their "equivalent" under parsimony: character weighting schemes. Our results are at odds with the typical view of phylogenomics, that is, that genomic-scale data sets will swamp out inferences from morphological data. Instead, weighting morphological data 2-10$\times $ in both likelihood and parsimony can in some cases "flip" which phylum is inferred to be the SOM. This typically results in the molecular hypothesis of Ctenophora as the SOM flipping to Porifera (or occasionally Placozoa). However, greater taxon sampling improves phylogenetic stability, with some of the larger molecular data sets ($>$200,000 characters and up to $\sim $100 taxa) showing node stability even with $\geqq100\times $ upweighting of morphological data. Accordingly, our analyses have three strong messages. 1) The assumption that genomic data will automatically "swamp out" morphological data is not always true for the SOM question. Morphological data have a strong influence in our analyses of combined data sets, even when outnumbered thousands of times by molecular data. Morphology therefore should not be counted out a priori. 2) We here quantify for the first time how the stability of the SOM node improves for several genomic data sets when the taxon sampling is increased. 3) The patterns of "flipping points" (i.e., the weighting of morphological data it takes to change the inferred SOM) carry information about the phylogenetic stability of matrices. The weighting space is an innovative way to assess comparability of data sets that could be developed into a new sensitivity analysis tool. [Metazoa; Morphology; Phylogenomics; Weighting.]., (© The Author(s) 2020. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.)

Placozoans, nonbilaterian animals with the simplest known metazoan bauplan, are currently classified into 20 haplotypes belonging to three genera, Polyplacotoma, Trichoplax, and Hoilungia. The latter two comprise two and five clades, respectively. In Trichoplax and Hoilungia, previous studies on six haplotypes belonging to four different clades have shown that their mtDNAs are circular chromosomes of 32-43 kb in size, which encode 12 protein-coding genes, 24 tRNAs, and two rRNAs. These mitochondrial genomes (mitogenomes) also show unique features rarely seen in other metazoans, including open reading frames (ORFs) of unknown function, and group I and II introns. Here, we report seven new mitogenomes, covering the five previously described haplotypes H2, H17, H19, H9, and H11, as well as two new haplotypes, H23 (clade III) and H24 (clade VII). The overall gene content is shared between all placozoan mitochondrial genomes, but genome sizes, gene orders, and several exon-intron boundaries vary among clades. Phylogenomic analyses strongly support a tree topology different from previous 16S rRNA analyses, with clade VI as the sister group to all other Hoilungia clades. We found small inverted repeats in all 13 mitochondrial genomes of the Trichoplax and Hoilungia genera and evaluated their distribution patterns among haplotypes. Because Polyplacotoma mediterranea (H0), the sister to the remaining haplotypes, has a small mitochondrial genome with few small inverted repeats and ORFs, we hypothesized that the proliferation of inverted repeats and ORFs substantially contributed to the observed increase in the size and GC content of the Trichoplax and Hoilungia mitochondrial genomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

In metazoans, Bcl-2 family proteins are major regulators of mitochondrially mediated apoptosis; however, their evolution remains poorly understood. Here, we describe the molecular characterization of the four members of the Bcl-2 family in the most primitive metazoan, Trichoplax adhaerens All four trBcl-2 homologs are multimotif Bcl-2 group, with trBcl-2L1 and trBcl-2L2 being highly divergent antiapoptotic Bcl-2 members, whereas trBcl-2L3 and trBcl-2L4 are homologs of proapoptotic Bax and Bak, respectively. trBax expression permeabilizes the mitochondrial outer membrane, while trBak operates as a BH3-only sensitizer repressing antiapoptotic activities of trBcl-2L1 and trBcl-2L2. The crystal structure of a trBcl-2L2:trBak BH3 complex reveals that trBcl-2L2 uses the canonical Bcl-2 ligand binding groove to sequester trBak BH3, indicating that the structural basis for apoptosis control is conserved from T. adhaerens to mammals. Finally, we demonstrate that both trBax and trBak BH3 peptides bind selectively to human Bcl-2 homologs to sensitize cancer cells to chemotherapy treatment., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Symbiotic relationships between eukaryotic hosts and bacteria range from parasitism to mutualism and may deeply influence both partners' fitness. The presence of intracellular bacteria in the metazoan phylum Placozoa has been reported several times, but without any knowledge about the nature of this relationship and possible implications for the placozoan holobiont. This information may be of crucial significance since little is known about placozoan ecology and how different species adapt to different environmental conditions, despite being almost invariable at the morphological level. We here report on the novel genome of the rickettsial endosymbiont of Trichoplax sp. H2 (strain "Panama"). The combination of eliminated and retained metabolic pathways of the bacterium indicates a potential for a mutualistic as well as for a parasitic relationship, whose outcome could depend on the environmental context. In particular we show that the endosymbiont is dependent on the host for growth and reproduction and that the latter could benefit from a supply with essential amino acids and important cofactors. These findings call for further studies to clarify the actual benefit for the placozoan host and to investigate a possible role of the endosymbiont for ecological separation between placozoan species.

Background: Periodic wellness assessments can provide an estimate of a person's relative risks for major diseases, but wellness visits are underused. Our suggestion is to use a comprehensive device during a single visit., Objective: The goal of this pilot study was to evaluate the feasibility of a novel one-stop wellness device (Preventiometer; iPEx5 GmbH, Greifswald, Germany) for performing multiple tests and providing a comprehensive wellness assessment in a short period., Methods: A Preventiometer was used to provide wellness assessments for 10 healthy volunteers who then answered a 25-question survey to rate their satisfaction with the testing and their overall impression., Results: All volunteers agreed or strongly agreed with the following: The assessment reports were easy to understand, the Preventiometer met their satisfaction, the participants were comfortable during the assessment, and all measurements and testing were well coordinated. Participants liked the instant test result feature. Most (90%) agreed that the machine was useful for a quick health assessment for busy people, and 70% felt that it was time efficient., Conclusion: In this feasibility pilot study, the Preventiometer performed multiple tasks and provided a comprehensive wellness assessment in a short period. Participants reported remarkably high satisfaction with the tests. A larger study is needed to prove that this is a pragmatic approach to help individuals improve their health., (© The Author(s) 2019.)

Background: Innate immunity provides the core recognition system in animals for preventing infection, but also plays an important role in managing the relationship between an animal host and its symbiont. Most of our knowledge about innate immunity stems from a few animal model systems, but substantial variation between metazoan phyla has been revealed by comparative genomic studies. The exploration of more taxa is still needed to better understand the evolution of immunity related mechanisms. Placozoans are morphologically the simplest organized metazoans and the association between these enigmatic animals and their rickettsial endosymbionts has recently been elucidated. Our analyses of the novel placozoan nuclear genome of Trichoplax sp. H2 and its associated rickettsial endosymbiont genome clearly pointed to a mutualistic and co-evolutionary relationship. This discovery raises the question of how the placozoan holobiont manages symbiosis and, conversely, how it defends against harmful microorganisms. In this study, we examined the annotated genome of Trichoplax sp. H2 for the presence of genes involved in innate immune recognition and downstream signaling., Results: A rich repertoire of genes belonging to the Toll-like and NOD-like receptor pathways, to scavenger receptors and to secreted fibrinogen-related domain genes was identified in the genome of Trichoplax sp. H2. Nevertheless, the innate immunity related pathways in placozoans deviate in several instances from well investigated vertebrates and invertebrates. While true Toll- and NOD-like receptors are absent, the presence of many genes of the downstream signaling cascade suggests at least primordial Toll-like receptor signaling in Placozoa. An abundance of scavenger receptors, fibrinogen-related domain genes and Apaf-1 genes clearly constitutes an expansion of the immunity related gene repertoire specific to Placozoa., Conclusions: The found wealth of immunity related genes present in Placozoa is surprising and quite striking in light of the extremely simple placozoan body plan and their sparse cell type makeup. Research is warranted to reveal how Placozoa utilize this immune repertoire to manage and maintain their associated microbiota as well as to fend-off pathogens.

Placozoans, together with sponges, are the only animals devoid of a nervous system and muscles, yet both respond to sensory stimulation in a coordinated manner. How behavioral control in these free-living animals is achieved in the absence of neurons and, more fundamentally, how the first neurons evolved from more primitive cells for communication during the rise of animals are not yet understood [1-5]. The placozoan Trichoplax adhaerens is a millimeter-wide, flat, free-living marine animal composed of six morphologically identified cell types distributed across a simple body plan [6-9]: a thin upper epithelium and a columnar lower epithelium interspersed with a loose layer of fiber cells in between. Its genome contains genes encoding several neuropeptide-precursor-like proteins and orthologs of proteins involved in neurosecretion in animals with a nervous system [10-12]. Here we investigate peptidergic signaling in T. adhaerens. We found specific expression of several neuropeptide-like molecules in non-overlapping cell populations distributed over the three cell layers, revealing an unsuspected cell-type diversity of T. adhaerens. Using live imaging, we discovered that treatments with 11 different peptides elicited striking and consistent effects on the animals' shape, patterns of movement, and velocity that we categorized under three main types: (1) crinkling, (2) turning, and (3) flattening and churning. Together, the data demonstrate a crucial role for peptidergic signaling in nerveless placozoans and suggest that peptidergic volume signaling may have pre-dated synaptic signaling in the evolution of nervous systems., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pbio.2005359.].

Placozoans are a phylum of nonbilaterian marine animals currently represented by a single described species, Trichoplax adhaerens, Schulze 1883. Placozoans arguably show the simplest animal morphology, which is identical among isolates collected worldwide, despite an apparently sizeable genetic diversity within the phylum. Here, we use a comparative genomics approach for a deeper appreciation of the structure and causes of the deeply diverging lineages in the Placozoa. We generated a high-quality draft genome of the genetic lineage H13 isolated from Hong Kong and compared it to the distantly related T. adhaerens. We uncovered substantial structural differences between the two genomes that point to a deep genomic separation and provide support that adaptation by gene duplication is likely a crucial mechanism in placozoan speciation. We further provide genetic evidence for reproductively isolated species and suggest a genus-level difference of H13 to T. adhaerens, justifying the designation of H13 as a new species, Hoilungia hongkongensis nov. gen., nov. spec., now the second described placozoan species and the first in a new genus. Our multilevel comparative genomics approach is, therefore, likely to prove valuable for species distinctions in other cryptic microscopic animal groups that lack diagnostic morphological characters, such as some nematodes, copepods, rotifers, or mites., Competing Interests: The authors have declared that no competing interests exist.

The phylum Placozoa officially consists of only a single described species, Trichoplax adhaerens, although several lineages can be separated by molecular markers, geographical distributions and environmental demands. The placozoan 16S haplotype H2 (Trichoplax sp. H2) is the most robust and cosmopolitan lineage of placozoans found to date. In this study, its genome was found to be distinct but highly related to the Trichoplax adhaerens reference genome, for remarkably unique reasons. The pattern of variation and allele distribution between the two lineages suggests that both originate from a single interbreeding event in the wild, dating back at least several decades ago, and both seem not to have engaged in sexual reproduction since. We conclude that populations of certain placozoan haplotypes remain stable for long periods without bisexual reproduction. Furthermore, allelic variation within and between the two Trichoplax lineages indicates that successful bisexual reproduction between related placozoan lineages might serve to either counter accumulated negative somatic mutations or to cope with changing environmental conditions. On the other hand, enrichment of neutral or beneficial somatic mutations by vegetative reproduction, combined with rare sexual reproduction, could instantaneously boost genetic variation, generating novel ecotypes and eventually species.

With the genomes available for many animal clades, including the early-branching metazoans, one can readily study the functional conservation of genes across a diversity of animal lineages. Ectopic expression of an animal protein in, for instance, a mammalian cell line is a generally used strategy in structure-function analysis. However, this might turn out to be problematic in case of distantly related species. Here we analyzed the GC content of the coding sequences of basal animals and show its impact on gene expression levels in human cell lines, and, importantly, how this expression efficiency can be improved. Optimization of the GC3 content in the coding sequences of cadherin, alpha-catenin, and paracaspase of Trichoplax adhaerens dramatically increased the expression of these basal animal genes in human cell lines.

Schierwater & DeSalle introduce the enigmatic phylum Placozoa., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Trichoplax adhaerens , the only known species of Placozoa is likely to be closely related to an early metazoan that preceded branching of Cnidaria and Bilateria. This animal species is surprisingly well adapted to free life in the World Ocean inhabiting tidal costal zones of oceans and seas with warm to moderate temperatures and shallow waters. The genome of T. adhaerens (sp. Grell) includes four nuclear receptors, namely orthologue of RXR (NR2B), HNF4 (NR2A), COUP-TF (NR2F) and ERR (NR3B) that show a high degree of similarity with human orthologues. In the case of RXR, the sequence identity to human RXR alpha reaches 81% in the DNA binding domain and 70% in the ligand binding domain. We show that T. adhaerens RXR (TaRXR) binds 9 -cis retinoic acid (9- cis -RA) with high affinity, as well as high specificity and that exposure of T. adhaerens to 9- cis -RA regulates the expression of the putative T. adhaerens orthologue of vertebrate L-malate-NADP + oxidoreductase (EC 1.1.1.40) which in vertebrates is regulated by a heterodimer of RXR and thyroid hormone receptor. Treatment by 9- cis -RA alters the relative expression profile of T. adhaerens nuclear receptors, suggesting the existence of natural ligands. Keeping with this, algal food composition has a profound effect on T. adhaerens growth and appearance. We show that nanomolar concentrations of 9- cis -RA interfere with T. adhaerens growth response to specific algal food and causes growth arrest. Our results uncover an endocrine-like network of nuclear receptors sensitive to 9 -cis -RA in T. adhaerens and support the existence of a ligand-sensitive network of nuclear receptors at the base of metazoan evolution., Competing Interests: Marta Kostrouchová is an Academic Editor for PeerJ. Authors declare there are no competing interests.

The phylum Placozoa holds a key position for our understanding of the evolution of mitochondrial genomes in Metazoa. Placozoans possess large mitochondrial genomes which harbor several remarkable characteristics such as a fragmented cox1 gene and trans-splicing cox1 introns. A previous study also suggested the existence of cox1 mRNA editing in Trichoplax adhaerens, yet the only formally described species in the phylum Placozoa. We have analyzed RNA-seq data of the undescribed sister species, Placozoa sp. H2 ("Panama" clone), with special focus on the mitochondrial mRNA. While we did not find support for a previously postulated cox1 mRNA editing mechanism, we surprisingly found two independent transcripts representing intermediate cox1 mRNA splicing stages. Both transcripts consist of partial cox1 exon as well as overlapping intron fragments. The data suggest that the cox1 gene harbors a single base pair (cytosine) micro exon. Furthermore, conserved group I intron structures flank this unique micro exon also in other placozoans. We discuss the evolutionary origin of this micro exon in the context of a self-splicing intron gain in the cox1 gene of the last common ancestor of extant placozoans.

The potential of DNA barcoding approaches to identify single species and characterize species compositions strongly depends on the marker choice. The prominent "Folmer region", a 648 basepair fragment at the 5' end of the mitochondrial CO1 gene, has been traditionally applied as a universal DNA barcoding region for metazoans. In order to find a suitable marker for biomonitoring odonates (dragonflies and damselflies), we here explore a new region of the CO1 gene (CO1B) for DNA barcoding in 51 populations of 23 dragonfly and damselfly species. We compare the "Folmer region", the mitochondrial ND1 gene (NADH dehydrogenase 1) and the new CO1 region with regard to (i) speed and reproducibility of sequence generation, (ii) levels of homoplasy and (iii) numbers of diagnostic characters for discriminating closely related sister taxa and populations. The performances of the gene regions regarding these criteria were quite different. Both, the amplification of CO1B and ND1 was highly reproducible and CO1B showed the highest potential for discriminating sister taxa at different taxonomic levels. In contrast, the amplification of the "Folmer region" using the universal primers was difficult and the third codon positions of this fragment have experienced nucleotide substitution saturation. Most important, exploring this new barcode region of the CO1 gene identified a higher discriminating power between closely related sister taxa. Together with the design of layered barcode approaches adapted to the specific taxonomic "environment", this new marker will further enhance the discrimination power at the species level.

The increase in atmospheric carbon dioxide (CO 2 ) leads to rising temperatures and acidification in the oceans, which directly or indirectly affects all marine organisms, from bacteria to animals. We here ask whether the simplest-and possibly also the oldest-metazoan animals, the placozoans, are particularly sensitive to ocean warming and acidification. Placozoans are found in all warm and temperate oceans and are soft-bodied, microscopic invertebrates lacking any calcified structures, organs, or symmetry. We here show that placozoans respond highly sensitive to temperature and acidity stress. The data reveal differential responses in different placozoan lineages and encourage efforts to develop placozoans as a potential biomarker system.