Biology subjects

Eisen, J.

Publications and source records attributed to Eisen, J..

6 recordsLinked to original sources

bioRxiv2022

GLOBAL HOST RESPONSES TO THE MICROBIOTA AT SINGLE CELL RESOLUTION IN GNOTOBIOTIC ZEBRAFISH

Resident microbes are a feature of vertebrate animals that influence diverse aspects of their biology from tissue development to metabolism. Here we describe transcriptional responses to the microbiota across all the cells of a model developing vertebrate, the larval zebrafish. By performing single cell transcriptomic analysis of whole germ free and conventionalized larvae, we show that the impacts of the microbiota are sensed by all major organ systems but that responses are highly specific to different cell types. The presence of microbiota stimulates the expansion of progenitor-like cells in epithelial tissues and increases proliferation gene expression in progenitor-like cell populations of the immune and nervous systems. Across many cell types, including enterocytes, immune cells, and neurons, the microbiota upregulates expression of genes involved in microbial responses, cell type-specific activities, and cell type-specific deployment of ATP metabolism genes. These combined transcriptional patterns demonstrate how the microbiota simultaneously modulate cellular immune and metabolic programs. The impacts of the microbiota on tissue development are illustrated by the exocrine pancreas, which in the absence of the microbiota is smaller and composed of uniformly differentiated acinar cells. The presence of the microbiota results in exocrine pancreas enlargement and heterogeneous cellular expression of digestive enzyme and secretion genes, demonstrating how the microbiota promotes plasticity in tissue development and function. This single cell transcriptional dataset demonstrates the impacts of the microbiota on vertebrate development across the body and provides a foundation for dissecting cell type specific responses to microbial consortia members or molecules. SummaryAnimal development proceeds in the presence of intimate microbial associations, but the extent to which different host cells across the body respond to resident microbes remains to be fully explored. Using the vertebrate model organism, the larval zebrafish, we assessed transcriptional responses to the microbiota across the entire body at single cell resolution. We find that cell types across the body, not limited to tissues at host-microbe interfaces, respond to the microbiota. Responses are cell-type specific, but across many tissues the microbiota enhances cell proliferation, increases metabolism, and stimulates a diversity of cellular activities, revealing roles for the microbiota in promoting developmental plasticity. This work provides a resource for exploring transcriptional responses to the microbiota across all cell types of the vertebrate body and generating new hypotheses about the interactions between vertebrate hosts and their microbiota.

developmental biology↗

bioRxiv2020

The microbiota promotes social behavior by neuro-immune modulation of neurite complexity

Host-associated microbiotas guide the trajectory of developmental programs, and microbial dysbiosis is linked to neurodevelopmental conditions such as autism spectrum disorder. Recent work suggests that microbiotas modulate behavioral phenotypes associated with these disorders. We discovered that the zebrafish microbiota is required for normal social behavior, and reveal a molecular pathway linking the microbiota, microglial remodeling of neural circuits, and social behavior in this experimentally tractable model vertebrate. Examining neuronal correlates of behavior, we found that the microbiota restrains neurite complexity and targeting of forebrain neurons required for normal social behavior and is necessary for localization of forebrain microglia, brain resident phagocytes that remodel neuronal arbors. The microbiota also influences microglial molecular functions, including promoting expression of the remodeling factor c1q, which we find is required for normal forebrain neurite complexity. Several distinct bacterial taxa are individually sufficient for normal microglial and neuronal phenotypes, suggesting that host neuroimmune development is sensitive to a feature common among many bacteria. Our results demonstrate that the microbiota influences zebrafish social behavior by stimulating microglial remodeling of forebrain circuits during early neurodevelopment, and suggest pathways for new interventions in multiple neurodevelopmental disorders.

neuroscience↗

bioRxiv2020

Late onset of Syt2a expression at synapses relevant to social behavior

As they form, synapses go through various stages of maturation and refinement. These steps are linked to significant changes in synaptic function, potentially resulting in changes in behavior. Here, we examined the distribution of the synaptic vesicle protein Synaptotagmin 2a (Syt2a) during development of the zebrafish nervous system. Syt2a is widely distributed throughout the midbrain and hindbrain early during larval development but very weakly expressed in the forebrain. Later in development, Syt2a expression levels increase, particularly in regions associated with social behavior, and most intriguingly, around the time social behavior becomes apparent. We provide evidence that Syt2a localizes to synapses on socially-relevant neurons in the ventral forebrain, co-localizing with tyrosine hydroxylase, a biosynthetic enzyme in the dopamine pathway. Our results suggest a maturation step for synapses in the forebrain that are spatiotemporally related to social behavior.

neuroscience↗

bioRxiv2019

Bacteria isolated from bengal cat (Felis catus x Prionailurus bengalensis) anal sac secretions produce volatile compounds associated with animal signaling

Anal sacs are an important odor producing organ found across the mammalian Order Carnivora. Secretions from the anal sac may be used as chemical signals by animals for behaviors ranging from defense to species recognition to signaling reproductive status. In addition, a recent study suggests that domestic cats utilize short-chain free fatty acids in anal sac secretions for individual recognition. The fermentation hypothesis is the idea that symbiotic microorganisms living in association with animals contribute to odor profiles used in chemical communication and that variation in these chemical signals reflects variation in the microbial community. Here we examine the fermentation hypothesis by characterizing volatile organic compounds (VOC) and bacteria isolated from anal sac secretions collected from a male bengal cat, a cross between a domestic cat and wild leopard cat (Felis catus x Prionailurus bengalensis).\n\nBoth left and right anal sacs of a male bengal cat were manually expressed (emptied) and collected. Half of the material was used to culture bacteria or to extract bacterial DNA and other half was used for VOC analysis. DNA was extracted from the anal sac secretions and used for a 16S rRNA gene sequence based characterization of the microbial community. Additionally, some of the material was plated out in order to isolate bacterial colonies. The same three taxa, Bacteroides fragilis, Tessaracoccus, and Finegoldia magna were abundant in the 16S rRNA gene sequence data and also isolated by culturing. Using Solid Phase Microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), we tentatively identified 52 compounds from bengal cat anal sac secretions and 67 compounds from cultures of the three bacterial isolates chosen for further analysis.. Among 67 compounds tentatively identified from bacteria isolates, 52 were also found in the anal sac secretion.\n\nWe show that the bacterial community in the anal sac consists primarily of only a few abundant taxa and that isolates of these taxa produce numerous volatiles that are found in the combined anal sac volatile profile. Many of these volatiles are found in anal sac secretions from other carnivorans, and are also associated with known bacterial biosynthesis pathways. This supports the fermentation hypothesis and the idea that the anal sac is maintained at least in part to house bacteria that produce volatiles for the host.

animal behavior and cognition↗

bioRxiv2018

Evolution of Endothelin signaling and diversification of adult pigment pattern in Danio fishes

Fishes of the genus Danio exhibit diverse pigment patterns that serve as useful models for understanding the genes and cell behaviors underlying the evolution of adult form. Among these species, zebrafish D. rerio exhibit several dark stripes of melanophores with sparse iridophores that alternate with light interstripes of dense iridophores and xanthophores. By contrast, the closely related species D. nigrofasciatus has an attenuated pattern with fewer melanophores, stripes and interstripes. Here we demonstrate species differences in iridophore development that presage the fully formed patterns. Using genetic and transgenic approaches we identify the secreted peptide Endothelin-3 (Edn3)--a known melanogenic factor of tetrapods--as contributing to reduced iridophore proliferation and fewer stripes and interstripes in D. nigrofasciatus. We further show the locus encoding this factor is expressed at lower levels in D. nigrofasciatus owing to cis-regulatory differences between species. Finally, we show that functions of two paralogous loci encoding Edn3 have been partitioned between skin and non-skin iridophores. Our findings reveal genetic and cellular mechanisms contributing to pattern differences between these species and suggest a model for evolutionary changes in Edn3 requirements across vertebrates.\n\nAuthor SummaryNeural crest derived pigment cells generate the spectacular variation in skin pigment patterns among vertebrates. Mammals and birds have just a single skin pigment cell, the melanocyte, whereas ectothermic vertebrates have several pigment cells including melanophores, iridophores and xanthophores, that together organize into a diverse array of patterns. In the teleost zebrafish, Danio rerio, an adult pattern of stripes depends on interactions between pigment cell classes and between pigment cells and their tissue environment. The close relative, D. nigrofasciatus has fewer stripes and prior analyses suggested a difference between these species that lies extrinsic to the pigment cells themselves. A candidate for mediating this difference is Endothelin-3 (Edn3), essential for melanocyte development in warm-blooded animals, and required by all three classes of pigment cells in an amphibian. We show that Edn3 specifically promotes iridophore development in Danio, and that differences in Edn3 expression contribute to differences in iridophore complements, and striping, between D. rerio and D. nigrofasciatus. Our study reveals a novel function for Edn3 and provides new insights into how changes in gene expression yield morphogenetic outcomes to effect diversification of adult form.

developmental biology↗

bioRxiv2018

Insights into the evolution of oxygenic photosynthesis from a phylogenetically novel, low-light cyanobacterium

Atmospheric oxygen level rose dramatically around 2.4 billion years ago due to oxygenic photosynthesis by the Cyanobacteria. The oxidation of surface environments permanently changed the future of life on Earth, yet the evolutionary processes leading to oxygen production are poorly constrained. Partial records of these evolutionary steps are preserved in the genomes of organisms phylogenetically placed between non-photosynthetic Melainabacteria, crown-group Cyanobacteria, and Gloeobacter, representing the earliest-branching Cyanobacteria capable of oxygenic photosynthesis. Here, we describe nearly complete, metagenome assembled genomes of an uncultured organism phylogenetically placed between the Melainabacteria and crown-group Cyanobacteria, for which we propose the name Candidatus Aurora vandensis {au.rora Latin noun dawn and vand.ensis, originating from Vanda}.\n\nThe metagenome assembled genome of A. vandensis contains homologs of most genes necessary for oxygenic photosynthesis including key reaction center proteins. Many extrinsic proteins associated with the photosystems in other species are, however, missing or poorly conserved. The assembled genome also lacks homologs of genes associated with the pigments phycocyanoerethrin, phycoeretherin and several structural parts of the phycobilisome. Based on the content of the genome, we propose an evolutionary model for increasing efficiency of oxygenic photosynthesis through the evolution of extrinsic proteins to stabilize photosystem II and I reaction centers and improve photon capture. This model suggests that the evolution of oxygenic photosynthesis may have significantly preceded oxidation of Earths atmosphere due to low net oxygen production by early Cyanobacteria.

microbiology↗